LIBRARY OF CONGRESS. 




UNITED STATES OF AMERICA. 



A GUIDE 



TO THE 



CLINICAL EXAMINATION 



OF 



THE BLOOD 



FOR DIAGNOSTIC PUBPOSES 



BY 

RICHARD C. CABOT, M.D. 



WITH COLORED PLATES AND ENGRAVINGS 



Second }£t)ition 



NEW YOEK 
WILLIAM WOOD AND COMPANY 
1897 



Copyright, 1897, 
By WILLIAM WOOD AND COMPANY. 



TO 



WILLIAM SIDNEY THAYEE, M.D., 

ASSOCIATE PROFESSOR OP MEDICINE IX J0H:N-S 
HOPKINS UNIVERSITY, 

IN GBATEFUL RECOGNITION OF THE STANDARD OF THOROUGH 
WORK ESTABLISHED BY HIM. 



PREFACE. 



In order to keep the size of this book within reasonable lim- 
its I have omitted all historical account of the steps by which 
our present knowledge of the different branches of the subject 
has been built up. 

Wherever it has seemed to me that a point was definitely 
established, I have stated the conclusions generally accepted 
without special reference to the names of those who worked 
them out. On the other hand, where our knowledge has seemed 
to be insufficient I have given some of the names and findings 
of those who are responsible for the opinions generally current. 

Theoretical discussions have been omitted on account of the 
strictly clinical plan of the book. 

The absence of any account of the origin of the blood cells, 
the chemistry of the blood, coagulation, and many other sub- 
jects of great scientific interest is due to the lack of any con- 
siderable clinical value in them so far as at present understood. 

The body of data referred to from time to time as the " Mas- 
sachusetts Hospital Blood Counts" consists of nearly four thou- 
sand blood examinations, about three thousand of which were 
made by Drs. Moffitt, Hewes, Joslin, Denny, Franklin White, 
Capps, and Barney — medical internes of the hospital since 1893. 
Permission to avail myself of these data was very kindly granted 
me by the visiting physicians of the hospital. To these I have 
added about one thousand examinations which I have made both 
within the hospital and outside. The technique used in all the 
four thousand examinations was essentially that described in 
the following pages. 

The accumulation of this body of facts and the great mass of 
foreign haematological literature (untranslated) have seemed to 
me sufficient reasons for the existence of this book — the first of 
its kind in English, so far as I am aware. Further, it has seemed 
to me a great pity that there should be no book available con- 



vi 



PREFACE. 



taining colored illustrations of stained blood preparations whicli 
bear some resemblance to their original, and are not wholly or 
partly works of the imagination (" diagrammatic'') . 

Funke, of Leipsic, has, I think, been as successful in dealing 
with the stained blood in the present work as he was with the 
fresh blood in the beautiful illustrations for W. S. Thayer's 
monograiDh on "The Malarial Fevers of Baltimore." 

Any one who writes on the blood must be constantly indebted 
to the following standard text-books: Hay em: "Du Sang," 
Paris, 1889. v. Limbeck : " Grundriss einer klinischen Patho- 
logie des Blutes," Jena, 1896 (second edition). Grawitz: 
"Klinische Pathologie des Blutes," Berlin, 1896. Schmaltz: 
"Pathologie des Blutes," Leipsic, 1896. Eieder: "Beitrage z. 
Kentniss der Leucocytosis," Leipsic, 1892. 

I have usually referred to them in the text as "Hay em," 
"Eieder," etc., always meaning one of the above works. 

The quotations from Schreiber in the text refer to manuscript 
notes of his lectures in 1896, kindly loaned to me by Dr. Mark 
W. Richardson. 

I am indebted to Dr. F. P. Henry for permission to use the 
cuts from his recent article on the filaria sanguinis hominis. 

December, 1896. 



PREFACE TO THE SECOND EDITION. 



A NEW chapter on the serum reaction in typhoid fever has 
been added, and the more obvious mistakes in the text have 
been corrected. I wish to express my thanks to those who have 
called my attention to mistakes in the text, especially to Dr. 
Joseph A. Capps, who has furnished many valuable sugges- 
tions. 

April, 1897. 
190 Marlborough Street, Boston. 



TABLE OF CONTENTS. 



BOOK I 
Introduction. 

Page 

Scope and Value of Blood Examination, S 

PAET I. 

Methods of Clinical Examination of the Blood. 

CHAPTER I. 



Examination of the Fresh Blood, . . . .' . . .5 

(a) Puncturing, . . ,5 

(6) Spreading the Blood, 7 

(c) Prevention of Cell Death, 8 

(d) Knowledge to be Gained from Fresh Blood, . . , . 8 

CHAPTER II. 

Counting the Corpuscles, 10 

(a) Sucking Up the Blood, 10 

(b) Diluting the Blood, 11 

(c) Adjusting the Diluted Blood in the Counting Chamber, . 13 

(d) Counting the Red Corpuscles, 14 

(e) Counting the White Corpuscles, 17 

(/) Counting both Red and White Corpuscles with One Pipette, . 18 



CHAPTER III. 

Centrifugalizing the Blood — Hemoglobin Estimation— Specific 
Gravity— Stained Specimens— Bacteriological Examina- 
tion, 

1. Daland's Haematocrit, Its Objects 

Use of the Haematocrit, 

2. Use of V. Fleischl's Hasmometer, 

Necessary Errors in Its Use, 



21 
21 
22 
26 
29 



viii TABLE OF CONTENTS. 

Page 

3. Specific Gravity Estimation, 29 

Hammerschlag's Method, 30 

4. Study of Dried and Stained Specimens, 31 

(a) Preparation of Cover-Glass Specimens, . • • .32 
(&) Fixing Cover-Glass Specimens, . . . • . 32 

(c) Staining, 33 

(d) Differential Counting (color analysis), . , • .34 

5. Bacteriological Examination, , . 35 

6. Other Methods of Examination, 36 

PAET II. 
Physiology of the Blood. 

CHAPTER IV. 

Morphology of Fresh Blood, 38 

(a) Appearances of Normal Red Corpuscles 39 

(&) Appearances of Normal White Corpuscles, . • , .40 

(c) Appearances of Normal Blood Plates, . . • , .41 

(d) Appearances of Fibrin Network, 41 

(e) Average Diameter of Red Cells, . . . . • .42 
(/) Normal Number of Red Cells 44 

Influence of Menstruation, Parturition, Lactation, • . 44 
Influence of Vasomotor Changes, ...... 44 

(g) Influence of Nutrition on the Red Cells, 45 

Influence of Fatigue on the Red Cells, 45 

(h) Normal Number of White Cells, 46 

(i) Normal Number of Blood Plates, 46 

CHAPTER V. 

Finer Structure of the Blood, . . . . . . .47 

1. Finer Structure of Red Cells, 47 

2. Finer Structure of White Cells and Their Varieties, • . 48 

(a) Lymphocytes 48 

(&) Transitional Cells, 49 

(c) Polymorphonuclear Neutrophiles, 49 

{d) Eosinophiles, 51 

<e) Basophiles, . 52 

Terminology, ......... 52 

Normal Percentage of Each Variety, . . . .53 

(/) Myelocytes, . 55 

Eosinophilic Myelocytes, 57 

Cornil's " Markcellen, " . 57 



TABLE OF CONTENTS. 



ix 



PART III. 
General Pathology of the Blood. 

CHAPTER VI. 

Page 

Unequal Distribution op the Blood— Plethora— Dilution and 

Concentration of the Blood, 59 

1. Unequal Distribution, 59 

2. Apparent Polycythsemia, 59 

(a) General Cyanosis, . ,60 

(&) Local Cyanosis, . .60 

(c) Feeble Circulation, 61 

3. Plethora — Serous or Cellular, 61 

4. Concentration of the Blood, " 62 

5. Dilution of the Blood, 64 

6. The Blood in High Altitudes, . . 65 

7. Phosphorus and CO Poisoning, 66 

8. Possibility of a True Plethora, 67 

CHAPTER VIL 

Anemia and Hydremia, . . . , 68 

(a) Pallor and Anaemia, 68 

(f>) "Tropical Anaemia," 69 

(c) Distinction Between Primary and Secondary Anaemia, . 69 

Secondary Anaemia, 71 

1. First Stage — Loss of Color, Weight, and Size, . . .71 
3. Second Stage — Poikilocytosis and Degeneration, , .71 

(a) Endoglobular Changes, 72 

(b) Crenation and Deformities ; Motility, . . .72 

(c) Changes in Staining Properties, . . . .73 

(d) Loss of Haemoglobin, . 73 

3. Third Stage — Deglobularization, 74 

4. Nucleated Red Corpuscles, 75 

(a) Normoblasts, 75 

(6) Megaloblasts, 76 

(c) Microblasts, 77 

(d) Atypical Varieties, 77 

Summary, . . . 79 

Hydraemia, 80 

CHAPTER VIIL 

Leucocytosis, Lymphocytosis, Eosinophilia, and Myelocytes, . 81 

Definition of Leucocytosis, 81 

Physiological Leucocytosis 83 



X 



TABLE OF CONTENTS. 



Page 

(a) Effects of Nutrition and Starvation, 83 

(£>) Digestion Leucocytosis, 84 

Its Diagnostic Value, 85 

(c) Leucocytosis of the New-Born, 86 

(d) Leucocytosis of Pregnancy, . . . . . .86 

(e) Leucocytosis after Parturition, 87 

(/) Leucocytosis from Exercise, Massage, and Baths, . . 87 
(g) Terminal Leucocytosis, 90 

Pathological Leucocytosis, 90 

(a) Post- hemorrhagic Leucocytosis, 91 

(b) Inflammatory Leucocytosis, 91 

(c) Toxic Leucocytosis, 94 

(d) Leucocytosis due to Therapeutic and Experimental In- 

fluences, 95 

Absence of Leucocytosis, 96 

Leucopenia, 96 

Lymphocytosis, 98 

Diagnostic Value of Lymphocytosis, . . . . .99 

Eosinophilia, 100 

Diminution of Eosinophiles, 102 

Diagnostic and Prognostic Value of Eosinophilia, . . . 103 
Myelocytes, 103 

CHAPTER IX. 

General Pathology op Hemoglobin and Fibrin, Lipemia, Mel- 
anemia AND Hemorrhage, . 106 

1. Haemoglobin and the " Color Index, " 106 

2. Fibrin, 107 

8. Lipsemia, 108 

4. Melanaemia, . . 109 

5. Hemorrhage, 109 

(a) Changes in the Blood Resulting from Hemorrhage, . . 109 

(6) Blood Regeneration, 110 

Regeneration of Red Cells, 110 

Blood Crisis, . . Ill 

Regeneration of White Cells, Ill 

Importance for Surgery of Blood Counting after Hemorrhage, . 112 
Chronic Hemorrhage 112- 



TABLE OF CONTENTS. 



xi 



BOOK 11. 
Special Pathology of the Blood. 

PART I. 
Diseases of the Blood. 

CHAPTER I. 

Page 

The Primary Anjemias, . .117 

1. The Blood in Pernicious Anaemia, 117-132 

1. Gross Appearances, 117 

2. Appearances of Fresh Blood, 117 

Red Cells and Hseraoglobin, 118 

Quantitative Changes, 118-121 

White Cells 121 

Quantitative Changes, ....... 121 

Blood Plates and Fibrin, 122 

Hgemoglobin, 123 

Qualitative Changes, . 123 

1. Red Corpuscles, 123 

(a) Increase in Diameter, 123 

(6) Deformities in Shape, 123 

(c) Staining Properties, 124 

(d) Nucleated Red Corpuscles, .... 124-126 

2. White Corpuscles, 126-129 

Characteristics of Pernicious An£emia, Summary, . . . 128 
Differential Diagnosis of Pernicious Anaemia, . . , 129 

1. Pernicious Anaemia and Chlorosis, .... 129 

2. Pernicious Anaemia and Malignant Disease, , . 129 

3. Pernicious Anaemia and other Secondary Anaemias, . 130 

4. Pernicious Anaemia and Leukaemia, .... 130 
Prognostic Value of the Blood in Pernicious Anaemia, . .131 

2. The Blood in Chlorosis, ........ 132 

The Blood in Gross, , , 133 

1. Red Cells and Haemoglobin, 133 

(a) Quantitative Changes, 133 

(b) Qualitative Changes, 136 

2. Specific Gravity, ,137 

3. White Cells, 137 

(a) Quantitative Changes, 137 

(&) Qualitative Changes, 138 

4. Blood Regeneration in Chlorosis, . . . . .138 

5. Summary and Diagnostic Value 139 



TABLE OF CONTENTS. 



CHAPTER II. 

Page 

Leukemia and Hodgkin's Disease, 140 

1. Splenic-Myelogenous Leukaemia, 140 

1. Red Cells, 141 

(a) Quantitative Changes, 141 

(&) Qualitative Changes, 142 

2. White Cells, 143 

(A) Quantitative Changes, 143 

(B) Qualitative Changes, 144 

(a) Myelocytes, 144 

(&) Adult Leucocytes, 145 

(c) Young Leucocytes, 146 

(d) Eosinophiles, 146 

2. Lymphatic Leukaemia, 147 

1. Red Cells, 148 

2. White cells, 148 

(a) Quantitative Changes, 148 

(5) Qualitative Changes, 149 

Summary of Blood Changes in Leukaemia, .... 150 
Differential Diagnosis of Leukaemic Blood, .... 151 

(a) From Hodgkin's Disease, 151 

(6) From Tumors in or near Spleen, 151 

(c) From Syphilitic or Tubercular Adenitis, . . . 151 

(d) From Hydronephrosis, 151 

(e) Fron] Leucocytosis, 151 

(/) From Chronic Malaria or Amyloid Disease, . .151 

Table of Differential Diagnosis in Leukaemia, . . . 152 
Effect of Intercurrent Infections in Leukaemia, . . . 152 

Hodgkin's Disease, , 154 

(a) Red Cells, 155 

(5) White Cells, 156 

(c) Summary and Diagnostic Value, . . • . 157 



PAET II. 
Acute Infectious Diseases. 

INTRODUCTION. 



Effects of Fever on the Blood, . . .... 158 

CHAPTER III. 

Pneumonia, Typhoid, and Diphtheria, 159 

I. Pneumonia, 159 

1. (a) Bacteriology of the Blood. ... 159 



TABLE OF CONTENTS. xiii 

Page 

(&) Coagulation and Fibrin, 159 

(c) Concentration of the Blood, 159 

2. Eed Cells, 160 

3. White Cells, 160 

(a) Quantitative Changes, 161 

(&) Qualitative Changes, 162 

4. Diagnosis and Prognosis, 164 

n. Typhoid Fever, . . . . . . . . . ,165 

1. Bacteriology and the Serum, . 165 

2. Red Cells and Haemoglobin, 166, 167 

3. White Cells, 167 

4. Effect of Complications on White Cells, . . . .169 

5. Qualitative Changes in the White Cells, .... 170 

6. Summary and Diagnostic Value, 171 

III. Diphtheria, 172 

(a) Red Cells, 172 

(5) Hemoglobin, .173 

(c) White Cells, .174 

(d) Summary 176 

CHAPTER IV. 

Acute Infectious Diseases (Continued). 

I. Scarlet Fever, 177 

(a) Red Cells, .......... 177 

(6) White Cells, 177 

(c) Summary and Diagnostic Value, ..... 178 

II. Measles, Rotheln, and Mumps, 179 

III. Small-pox (Variola), 180 

IV. Acute Articular Rheumatism, 180 

(a) Fibrin, Alkalinity, Red Cells, . . . . . .181 

(6) White Cells in Acute Forms, . . . . . .182 

(c) White Cells in Subacute Forms, ...... 183 

(d) White Cells in Chronic and Muscular Forms, . , . 183 

(e) Summary and Diagnostic Value, 184 

V. Asiatic Cholera, 184 

VI. Erysipelas, 185 

VII. Tonsillitis, 186 

VIII. Grippe, .187 

IX. Septicaemia, 188 

(a) Bacteriology of the Blood, - 188 

(6) Red Cells, 190 

(c) White Cells, 191 

(d) Summary and Diagnostic Value, ..... 193 

X. Abscess, 195 

A. Appendicitis, ......... 195 

(a) Leucocytosis, ....... 198-201 



xiv TABLE OF CONTENTS. 

Page 

(&) Significance of the Absence of Leucocytosis, . , 199 
(c) Differential Diagnosis, 201 

B. Pus Tube, Pelvic Abscess, and Pelvic Peritonitis, . . 203 

Differential Diagnosis, , 204 

C. Otitis Media 205 

D. Osteomyelitis, 205 

E. Other Abscesses, 206 

Diagnostic Value, 207 

XI. Gonorrhoea, 207 

XII. Yellow Fever, . . . 208 

XIII. Typhus Fever, 208 

XIV. Relapsing Fever, 209 

XV. Glanders, = 209 

XVI. The Bubonic Plague, 209 

XVII. Actinomycosis, ......... 209 

XVIII. Trichinosis, 209 

CHAPTER V. 

Diseases Affecting the Serous Membranes, 210 

I. Serous Pleurisy, 210 

(a) Summary and Diagnostic Value, 212 

(&) Purulent Pleurisy (Empyema) , 213 

II. Peritonitis, . 213 

Diagnostic Value, 214 

III. Pericarditis (with Effusion), 214 

Diagnostic Value, .... .... 215 

IV. Meningitis, 215 

Diagnostic Value, 216 



PAET III. 
Chronic Infectious Diseases. 



CHAPTER VI. 

Tuberculosis, Syphilis, and Leprosy, 217 

I, Tuberculosis, 217 

1. Red Cells and Haemoglobin, 217 

(a) Quantitative Changes, .... ... 217 

(b) Qualitative Changes, 218 

2. Leucocytes, 219 

(a) Changes in Phthisis, ....... 219 

(b) Changes in Bone Tuberculosis and Cold Abscess, . 223 

(c) Changes in Acute Miliary Tuberculosis, . . . 225 

(d) Changes in Tubercular Peritonitis, » . . . 227 



TABLE OF CONTENTS. XV 

Page 

(e) Changes in Tubercular Meningitis, .... 228 
(/) Changes in Tubercular Pericarditis, .... 230 
ig) Changes in Tubercular Pleurisy, .... 230 
(/i) Changes in Glandular Tuberculosis, .... 230 
(i) Changes in Genito-Urinary Tuberculosis, . . . 231 

II. Syphilis, 231 

1. (a) Changes in Red Cells and Haemoglobin, . . . 231 
(&) Justus' Reaction, . . . . . . . , 233 

2. Changes in White Cells, . . . . . . .233 

Diagnostic Value, 234 

III. Leprosy 234 

PAKT lY. 
Diseases of Special Organs. 

CHAPTER VII. 

Diseases of the Digestive Organs, 236 

I. Diseases of the Stomach, 237 

(a) Peptic Ulcers — Gastric or Duodenal, .... 237 

1. Red Cells, 237 

2. White Cells, 240 

(6) Gastritis and Dyspepsia, 240 

(c) Chronic Gastritis, 241 

(d) Hyperacidity and Hypersecretion, 242 

(e) Dilated Stomach, 243 

(/) Corrosive Gastritis, 243 

II. Diseases of the Intestines, 243 

Influence of Saline Cathartics on the Blood, .... 243 

(a) Acute Enteritis, 244 

(&) Chronic Diarrhoea, . . . . . , . . 244 
(c) Intestinal Obstruction, 245 

III. Diseases of the Liver, 246 

(a) Catarrhal Jaundice, . 246 

Qualitative Changes of Red Cells, 247 

Summary and Diagnostic Value, 247 

(6) Cirrhosis of the Liver, . . . . . . . 247 

1. Ordinary (Atrophic) Cirrhosis without Jaundice, . 248 

Qualitative Changes of Red Cells and Hsemoglobin, . 248 
White Cells, ........ 248 

2. Hypertrophic Cirrhosis with Jaundice, . . . 249 

Red Cells and Haemoglobin, 250 

White Cells, 250 

Diagnostic Value, 251 

(c) Hydatid Cyst of the Liver 251 

(d) Acute Yellow Atrophy of the Liver, .... 251 



xvi TABLE CONTENTS. 

Page 

(e) Phosphorus Poisoning, 251 

(/) Chol^mia, 252 

(g) Gall-stones, 252 

(h) Cholangitis, . 253 

ii) Abscess of the Liver, 253 

(j) Cancer of the Liver, 253 

(k) Gumma of the Liver, 254 

Diseases of the Heart, 254 

(a) Pericarditis, . 254 

(b) Endocarditis, . . . 254 

Red Cells, 254 

White Cells, 255 

Diagnostic Value, ........ 255 

(c) Myocarditis, .256 

(d) Valvular Heart Disease, 256 

Red Cells, 256 

White Cells, . 257 

(e) Congenital Heart Disease, 250 

Diseases of the Kidneys, 259 

(a) Acute Nephritis, 260 

Red Cells and Haemoglobin, ...... 260 

White Cells, . , 261 

(5) Chronic Diffuse Parenchymatous Nephritis, . . . 261 

Red Cells and Haemoglobin, 261 

White Cells, 263 

(e) Chronic Interstitial Nephritis, ...... 264 

(d) Pyelo-nephritis, 265 

(e) Stone in the Kidney, . . . . . . . .265 

Diagnostic Value, 266 

(/) Floating Kidney, 266 

Diseases of the Lungs, .' . 266 

(a) Bronchitis, 266 

(1) Acute Bronchitis, 266 

(2) Chronic Bronchitis, 267 

(6) Emphysema aud Asthma, . , . . . . . 268 

PAET V. 

Diseases of the Neryous System, Constitutional Diseases 

AND HeMOREHAGIC DISEASES. 
CHAPTER VIII. 

Diseases of the Nervous System, ....... 270 

1. Neuritis, 270 

(a) Acute Multiple Neuritis, 270 

(&) Alcoholic Neuritis, 270 



TABLE OF CONTENTS. Xvii 

Park 

2. Neuralgia, • . . 371 

3. Diseases of the Brain, ....... 271 

(a) PachymeniDgitis, ....... 271 

(6) Cerebral Syphilis, ........ 271 

(c) Cerebral Tumor, 271 

(d) Cerebellar Tumor, 271 

4. Chorea, , 271 

5. Chronic Diseases of the Spinal Cord, 271 

Tabes Dorsalis, » .... 271 

Syringomyelia, 271 

Spastic Paraplegia, 271 

Diffuse Myelitis, 271 

Paralysis Agitans, . 271 

Progressive Muscular Atrophy, 271 

6. General Paralysis of the Insane, 271 

7. Hysteria, Neurasthenia, and Hypochondriasis, . , . 272 

8. Mental Diseases . 273 

Constitutional Diseases, 274 

(1) Obesity, 274 

(2) Diabetes, 274 

Red Cells, 274 

White Cells, 275 

(3) Gout, . .275 

(4) Myxoedema, 276 

(5) Graves' Disease, 277 

(fi) Addison's Disease, . , 277 

(7) Osteomalacia 278 

(8) Rickets, 279 

CHAPTER IX. 

Blood Destruction and Hemorrhagic Diseases 281 

I. Hemorrhagic Diseases, 281 

1. Purpura Hsemorrhagica 281 

2. Scurvy and Barlow's Disease, 281 

3. Hsemopbilia, 282 

II. Blood Destruction, .282 

1. Haemoglobinaemia in Infectious Diseases, .... 282 

2. Paroxysmal Hsemoglobinsemia, ...... 282 

3. Burns, Snake Poison, etc., = 283 

4. Poisons, Chlorate of Potash, Antipyretics, etc., . . 284 

5. Illuminating Gas, .... .... 284 

6. Tansy Poisoning, 386 



xviii 



TABLE OF CONTENTS. 



PAET YI. 

Malignant Disease, Blood Parasites, and Intestinal 
Parasites. 



CHAPTER X. 

Page 

Malignant Diseases, 287 

1. Cancer, 287 

L Red Cells, 287 

(a) Quantitative Changes, 287 

lb) Haemoglobin, 290 

(c) Regeneration of Blood after Operations on Cancer- 
ous Growths, ........ 291 

(d) Qualitative Changes in Red Cells, .... 292 
II. White Cells, 293 

(a) Influence of Position and Size of Tumor, . . . 293 

(5) Influence of Individual Constitution, . . . 295 

(c) In Cancer of the Breast, 295 

(d) In Cancer of the Stomach, 296 

(e) Digestive Leucocytosis in Gastric Cancer, . , . 298 

(f) Effect of Metastases in Gastric Cancer, . . . 299 

(g) In Cancer of the Gullet, 300 

(h) In Cancer of the Liver, ...... 30Q 

(i) In Cancer of the Intestine, 301 

(/) In Cancer of Omentum and Abdominal Organs Gener- 
ally, 302 

{Jc) In Cancer of the Kidney, . . . . . .302 

(Z) In Cancer of the Uterus, . . . . . .803 

(m) In Cancer of other Organs, 304 

Qualitative Changes of Leucocytes in Cancer, . . . . 305 

(a) Adult Cells, 305 

(b) Eosinophiles, 305 

(c) Myelocytes, 805-307 

2. Sarcoma, . 307 

Red Cells and Haemoglobin, 307 

White Cells in, 809 

Qualitative Changes of Leucocytes in Sarcoma, . . . 310 
(a) Adult Cells, 810 

(6) Eosinophiles 310 

(c) Myelocytes, 311 

Summary and Diagnostic Value, 312 

CHAPTER XI. 

Blood Parasites and Intestinal Parasites, 315 

1. Examination for the Plasmodium Malarias and Its Products, . 315 
I. Time of Examination, 315 



TABLE OF CONTENTS. Xix 

Page 

II. Method of Examination, .315 

III. The Malarial Organism Described, 316 

(a) Eecognition of Hyaline Forms, ..... 316 
(6) Pigmented Forms, 317 

(c) Segmentation, 319 

(d) Flagella and Pigmented Leucocytes, .... 320 

(e) Crescents, 321 

IV. Staining the Malarial Organism, 322 

V. Other Changes in the Blood 324 

Red Corpuscles, 324 

Haemoglobin, 325 

White Cells, 326 

2. Filaria Sanguinis Hominis, ....... 326 

3. Spirochaote of Relapsing Fever, 331 

Technique of Examination, 332 

4. Distomum Haematobium, 333 

5. Bacteria in the Blood, 333 

(a) Cover-Glass Specimens, 333 

(h) Cultures, 333 

Anaemia due to Intestinal Parasites, 333 

CHAPTER XIL 

The Blood in Infancy, 335 

(a) General Characteristics, 335 

(b) The Anaemias of Infancy 337 

1. Classification, 337 

2. Secondary Anaemias, 338 

3. "Anaemia Infantum Pseudoleukaemica," .... 341 

4. Importance of the Term as Indicating the Difficulty of 

Classifying the Anaemias of Infancy 343 

5. Pernicious Anaemia in Infancy, 343 

6. Leukaemia in Infancy, 346 

PAET YII. 
Examination of the Serum. 

CHAPTER XIII. 

The Clump Reaction, ... ..o e ... 348 

1, General Description, «... 348 

2. Technique, . . . . . . . . . . .350 

(a) The Body Fluids Used, ....... 350 

(5) Use of the Whole Blood—Fluid, ...... 351 

(c) Use of the Whole Blood— Dried, 353 

(d) Use of the Serum— Fluid ; Quick Method, . . .354 

(e) Use of the Serum— Fluid ; Slow Method, . . . .354 



XX 



TABLE OF CONTENTS. 



Page 

(/) Use of Blister Fluid, 356 

(g) Relative Advantages of the Slow and of the Quick Method, 357 

(h) The Cultures to be Used, 357 

(i) The Use of Suspensions instead of Cultures, . . . 359 

(J) The Use of Attenuated Cultures, 359 

(&) The Clump Reaction with Dead Bacilli, . . . .359 
(I) Dilution and the Time Limit, ...... 360 

3. Sero Diagnosis of Typhoid Fever, 362 

(a) General Statistics, ........ 365 

(6) How Early does the Reaction Appear? .... 365 

(c) How Late does the Reaction Last? ..... 366 

{d) The Intensity of the Reaction, 367 

(e) Effects of Sera of Other Diseases on Typhoid Bacilli, . 368 
(/) Summary of Negative Results, ...... 369 

4. Effects of Typhoid Serum on Other Bacilli, . . . .370 

(a) On the Bacillus Coli Communis, 370 

(&) On the Bacillus Enteritidis (Gartner), . . .371 

(c) On the Bacillus of Psittacosis, 371 

id) On the Klebs-Loeffler Bacillus and Pus Cocci, . . .371 
(e) Summary of Clinical Evidence, 371 

5. Sero -Diagnosis of Other Diseases, ...=,.. 372 

(a) Cholera, 372 

(b) Pyocyaneus Infections, 372 

(c) Diphtheria, . 372 

(d) Pneumococcus Infections 372 

(e) Colon Bacillus Infections, . , . ^ . . . 373 
(/) Malta Fever, . 374 

(g) Peripneumonia of Cattle, and Hog Cholera, . . . 374 

(h) Proteus Infections, 374 

(i) Oidium Albicans, , . 374 

{j} Miscellaneous Reports on Scaiiet Fever, Tetanus, Septi- 
caemia, and Psittacosis, 375 

6. The Nature of the Clump Reaction, ...... 375 

7. The Nature of the Clumping Substance, 376 

8. Sero-Prognosis, 377 

9. Bibliography, 426 

Appendix— Neusser's "Perinuclear Basophilic Granules," . . .378 

Bibliography, 379 

Index, 430 



BOOK I. 



INTRODUCTION. 



SCOPE AND VALUE OF BLOOD EXAMINATION. 

HEMATOLOGY is stiU SO new a study that no confident state- 
ment can be made as to the exact limits of its usefulness in the 
practice of medicine. It has solved some problems where least 
was hoped from it, and given us disappointingly little help 
where great expectations had been aroused. We might have ex- 
pected from it some light on the nature of rheumatism, furun- 
culosis, uraemia, diabetes, but none has come. 

On the other hand, who could have hoped that it would help 
us in the diagnosis of central pneumonia, of deep-seated sup- 
purations and ovarian tumors, etc., or in the prognosis of post- 
scarlatinal nephritis or of pneumonia? 

There are probably not more than five or six diseases in 
which the blood examination gives us the diagnosis ready-made, 
but there is a very considerable number of conditions in which 
the blood examination will help us to make it. Not pathogno- 
monic signs, but links in a chain of evidence are what we are to 
expect from blood examination. Yery often the simple discov- 
ery that the blood is normal may be a fact of the greatest value 
in diagnosis. 

On the whole it seems to me that the examination of the 
blood gives evidence similar in kind and not much inferior in 
value to that obtained by examination of the urine. Both 
methods of examination give us (a) a ready-made diagnosis in 
a few diseases ; (b) side lights on a good many obscure condi- 
tions ; and (c) the frequently great assistance of a negative re- 
port. In certain wards of the Massachusetts General Hospital 
it has been for some years the rule to examine the blood of 
every patient as a matter of routine at the time of entrance. In 
a small proportion of cases this gave negative evidence only ; in 
a much larger proportion it materially assisted in the making of 
a diagnosis. 



4 



INTRODUCTION. 



Improvements in technique have lessened the labor and in- 
creased the accuracy of blood examination. The most important 
facts about the blood of nearly every case can be obtained by 
a practised observer in fifteen minutes. The experiments of 
Reinert and others have shown that with due care no error suffi- 
cient to mislead judgment need occur. 

The blood is the only tissue that we can study easily during 
the life of the patient. Its relations to all other tissues are such 
that it is typical of them all in a way that no other tissue is, act- 
ing on all and being acted on by all. As yet we have studied 
chiefly its morpliologj^, and from that single aspect obtained 
most of the clinically valuable information which we possess 
about it. But the field of the blood chemistry is in many re- 
spects even more promising at the present time, and there seems 
reason to believe that the stud^^ of the blood is still in its in- 
fancy and will take a higher place in the future as an aid to diag- 
nosis, prognosis, and treatment. 

Like all methods of physical examination it has especial use- 
fulness when we cannot communicate with a patient, either by 
reason of his unconsciousness, stupidity, or insanity, or because 
he speaks no widely used language. In such cases the detec- 
tion of a marked anaemia, a leucocytosis, or a malarial organism 
may be of the greatest assistance. Malingering is often made 
more difficult by it, and in the differentiation of organic from 
functional disease it is often very helpful. There is no febrile 
disease on which it may not throw light. 

The evidence for these and many other aids furnished by the 
blood examination in clinical work is given in the later chapters 
of this work. 



PART I. 



METHODS OF CLINICAL. EXAMINATION OF 
THE BLOOD. 



CHAPTEE I. 

COKFINING ourselves to the clinically available processes by 
which we can gain information of diagnostic or prognostic 
value, blood examination at the present time embraces seven 
processes. 

1. Examination of the fresh blood (with or without a warm 
stage). 

2. Counting the red and the white corpuscles. 

3. Estimation of the relative volumes of corpuscles and plasma 
by centrifugalizing the blood. 

4. Estimation of the amount of coloring matter. 

5. Estimation of the specific gravity of the blood. 

6. Examination of dried and stained specimens. 

7. Bacteriological examination of the blood. 

To describe these processes in detail is the purpose of the 
next chapters. 

I. Examination of the Fresh Blood. 

(a) Obtaining the hlood hy 'puncture. In all the processes 
about to be described, except the bacteriological examination, 
the first step is as follows : 

Wipe off the lobe of the patient's ear with a damp cloth and 
then rub it with a dry one. This serves to remove gross dirt 
and also to make the tissues hypersemic, so that a slight punc- 
ture will draw blood. Attempts to sterilize the skin, or washing 
it with alcohol and ether, are unnecessary. 

Use a three-sided (bayonet-pointed) surgical needle or a small 
lancet — a sewing needle, even a sharp one, gives more pain and 



6 



CLINICAL BLOOD EXAMINATION. 



draws less blood from a given depth of puncture. The needle 
need not be sterile. In several thousand blood counts made at 
the Massachusetts General Hospital since 1893 the needles have 
never been sterilized and no signs of sepsis have been seen in 
any case. 

Possibly this is due in part to the fact that the next step in 
the process after the puncture has been made is always to wipe 
away four or five successive drops as they emerge, which serves 
not only to get the blood flowing freely, but also to wash the ear 
in its own blood. 

The puncture is best made into the lower surface or edge of 
the lobe, which is steadied with the fingers of the left hand. A 
very quick stroke gives least pain, the hand rebounding like a 
piano hammer. If the skin of the lobe is stretched tight with 
the fingers of the left hand so that no "give" is possible, the 
quick puncture gives hardly any pain. I have repeatedly taken 
blood from a sleeping child without waking it. What hurts the 
patient is the mistaken tenderness that slowly presses the needle 
through the skin. The puncture must be deep enough to make 
the blood flow freely and without pressure, after it is once 
started by pressing out a few drops. Blood squeezed out with 
pressure should never be used for counting, as it is likely to be 
considerably diluted with fluid pressed out of the neighboring 
tissues. If the skin is moderately thin and the ear easily made 
hyperaemic, a puncture one-eighth of an inch deep is suflicient. 
With thick, bloodless skin it may be necessary to go in one- 
quarter or one-third of an inch — never more. Beware of bleeders. 
I have seen bleeding from a puncture made for a blood count 
which could not be checked for three-quarters of an hour. It is 
always safer to ask after a history of hsemophilia as a matter of 
routine before taking blood, just as one asks after false teeth 
before etherizing. If there is a history of haemophilia, a mere 
touch of the needle point will give us all the blood we need 
without embarrassing us with a troublesome hemorrhage. 

There is no question, I think, as to the superiority of the ear 
over the finger for drawing the drop of blood. The ear is de- 
cidedly less sensitive than the finger, and a slighter puncture 
gives us all the blood we need. Moreover, it is often a distinct 
advantage, especially in children, that the patient cannot watch 
the puncture of the ear, or the preparations for making it. A 



METHODS OF CLINICAL EXAMINATION. 



7 



sleeping patient often needs to be roused to get at his finger, 
while his ear is usually easily accessible above the bed clothes. 
Again, the absence of any bony prominence against which to 
press makes us less likely to use too much pressure than if we 
puncture the finger. 

When one is making frequent examinations of the blood of a 
sensitive person, as in pneumonia, these details are of real im- 
portance, and in cases of pernicious anaemia in which the pre- 
vious attempts to get blood from the finger had been absolute 
failures, I have found no difficulty in getting it from the ear. In 
this disease the advantages of the ear over the finger are pecu- 
liarly great. 

Spreading ihe Blood. 

{b) When, after wiping away the first four or five drops, a 
good-sized drop exudes spontaneously, touch the centre of a 
perfectly clean cover-glass against the 

summit of the drop ivitlioid toucMng — ~— -^T"""^'^ 

the shin itself at all, and drop the / , 

cover-glass face downward upon a / / 
slide so that the force of the impact ^^-.^^J^ ^ 

will help to spread the drop of blood 
thinly and evenly between slide and 
cover. It is recommended by Thayer 
and others to hold the cover-glass i -Proper Method of how- 

. . ing a Cover Glass. 

With lorceps, but there is no harm m 

holding it with the fingers, provided we avoid touching either 
of its surfaces, i.e., hold it alw^ays as in Fig. 1. 

Slide and cover must be perfectly clean, else the blood will 
not spread out in a layer thin enough to avoid the corpuscles 
overlying each other so that not one of them is clearly seen. 
Further, as dirt simulates fairly closeh^ some of the pathological 
appearances for which we are on the lookout, its presence on the 
slide leads to loss of time or to mistaken conclusions. Cover- 
glasses, as they come from the shops, are usually coated with a 
substance not easily to be removed. To get them really clean 
nothing is so simple as or more effective than soap and water. 
After several years' use of the method of cleaning usually ad- 
vised (viz., strong mineral acid, followed by alcohol and then by 
ether) , I have become converted to the use of plain soap and 



8 



CLINICAL BLOOD EXAMINATION. 



water as the best and simplest way of cleaning slides or cover- 
glasses. Kub soap over every part of the glass, wash it oif thor- 
oughly with water, and polish it with a clean handkerchief 
(most towels are apt to leave a scrap of lint on the glass) . If 
slide and cover are perfectly clean, are held as in Fig. 1, and al- 
lowed to touch only the summit of the blood drop and not the 
skin, the blood will spread out properly between them, and no 
pressure on the cover-glass will be needed to make the layer of 
corpuscles thin enough. Pressure is undesirable, as it often 
makes all sorts of artefacts in the preparation and hastens cre- 
nation of the red corpuscles. Better results are obtained if 
slide and cover are ivarmed just before using. 

Prevention of Cell- Death. 

Slides so prepared are usually best examined with a one- 
iwelfth oil-immersion lens. As a rule they keep long enough 
for purposes of examination without any further precautions, 
but if we desire to keep the blood fresh and uncoagulated for a 
longer period, it is best to exclude air in this way : Paint upon 
the slide with vaseline, cedar oil, or any gummy substance a 
hollow square or ring of about the size of the cover-glass, so 
that when the latter with its drop of blood is put down upon 
the slide the drop will spread out inside the ring of oil, which 
seals the margins of the cover-glass to the slide. Specimens so 
prepared will keep for many hours unchanged, and without cre- 
nation or coagulation, if the weather is warm or if the slide be 
kept in a warm place. 

In examining blood suspected of containing malarial para- 
sites it is sometimes useful to put the whole microscope into 
one of the warming apparatuses devised for the purpose. This 
is better than any of the various kinds of warm stage in use, but in 
clinical work there is rarely if ever any need for artificial heating 
apparatus of any kind, provided the room and the slide are warm. 

What Can he Learned from Fi^esh Blood. 

Examination of the fresh blood by the method just described is 
the best way known for ascertaining the presence or absence of — 

1. The Plasmodium malari*. 

2. The Spirochsete of relapsing fever. 



METHODS OF CLINICAL EXAMINATION. 



9 



3. Tlie Filaria saDguinis liominis. 

4. Kouleaux formation among the red cells. 

It is also a quick and convenient method of finding out with 
approximate accuracy : 

(a) Whether the blood contains an increased amount of fibrin ; 

(b) Whether any considerable anaemia or leucocytosis* is 
present ; 

(c) Whether or not the amount of hsemoglobin in the red 
cells is much decreased; 

(d) Whether the red corpuscles are deformed ; 

(e) Whether the " blood plates" are increased or not. 

A practised observer can also make a diagnosis of leukaemia by 
this method in most cases, but here mistakes may easily occur. 

So much can sometimes be learned from a specimen pre- 
pared in this very quick and easy way that it should be as much 
a matter of routine as a urine examination. But in order to get 
any information from such a preparation we must previously 
have familiarized ourselves with the appearance of normal blood 
under such conditions — with the size, shape, color, and refrac- 
tions of the red cells, white cells, and blood plates and their ratio 
to one another, and with the great variety of curious phenomena 
to be seen as a drop of blood gradually dries up between slide 
and cover. No book can teach this: it must be learned by 
actual experiment. 

Some of the commoner sources of error will be referred to 
later. Here I will mention only the Brownian movement in the 
protoplasm of the corpuscles, to be distinguished clearly both 
from the amoeboid movements of the leucocytes or of the malarial 
parasite and also from the irregular contractions of the dying 
protoplasm, which give rise to pseudo-amceboid motions in the 
crenated points of normal red cells or in the irregular projections 
of corpuscles deformed by disease (vide wfra) . 

For a more detailed description of normal red corpuscles, 
white corpuscles, and blood plates the reader is referred to 
Part II. 

An account of the pathological changes to be observed in the 
fresh blood will be given in later chapters. 

* More accurately it is only the ratio of red to white corpuscles tliat 
we can determine, and when the red are very much diminished in num- 
ber we may be deceived into supposing that the white are increased. 



CHAPTER II. 



COUNTING THE CORPUSCLES. 



Out of the many instruments devised for this x^urpose that 
of Thoma-Zeiss is so much the most commonl}^ used and most 

accurate that I shall men- 
tion no other. In the use of 
this instrument there are five 
steps or stages : 

1. Puncturing the ear. 

2. Diluting and mixing 
the blood thus obtained. 

3. Adjusting a drop of di- 
luted blood in the counting 
chamber. 

4. Counting the corpuscles. 

5. Cleaning the pipette. 
To count the white corpus- 
cles, a different instrument is 
often used from that em- 
ployed for the red. 

The technique is nearly 
the same for both instru- 
ments, but for clearness' sake 
I shall describe them sepa- 
rately. To save time I shall 
call the small-bore i^ipette 
used for red corpuscles (Fig. 
2, A) the "red counter," and 
the large-bore pipette (Pig. 
2, B) the "white counter." 



3 



f 



Fig. 2.— Thoma-Zeiss Pipettes. ^4, For red cor- 
puscles; i?, for white corpuscles. 



Counting the Bed Corpuscles. 

(a) After puncturing the ear as above described, and as soon 
as the blood is flowing freely, put the point of the " red counter" 



COUNTING THE CORPUSCLES. 



11 



into the drop as it emerges from the ear, and by sucking gently 
on the rubber tube attached to the other end, draw up blood to 
the mark 0.5 on the pipette. It needs some practice to stop 
exactly at the mark, but if we happen to draw the blood up a 
little past the mark 0.5 no considerable error results, provided 
we draw the column down again to the mark by tapping the 
point of the pipette on a towel, and provided also that the in- 
strument is perfectly clean and dry. The aim and intention, 
however, should always be to stop exactly at the mark 0.5, and 
with a little practice we can do it, except with nervous or deliri- 
ous patients, and those who carelessly move the head just at the 
critical moment. With such patients we usually have to con- 
tent ourselves with drawing the blood a little beyond the mark 
0.5 and then drawing it down again to the mark as above de- 
scribed. 

Diluting the Blood. 

(b) The bottle of solution to be used for diluting the blood 
should be ready uncorked at the bedside. Of the many solutions 
suggested by various authors none is better than Gowers\ the 
formula for which is as follows : 

Sodii sulphat. , gr. 104 

Acid, acetic, . . . . . 3 i. 
Aquae, ad | iv. 

Toisson's solution is also very useful and stains the white 
corpuscles so that they can be easily distinguished from the 
red. Its composition is as follows 



Methyl violet, 5 B, 
Sod. chlor. , 
Sod. sulph., 
Neutral glycerin, 
AquaB destill. , 



. 025 gm. 
1.000 " 
8.000 " 
30. 000 cm. 
160.000 cm. 



We must wait about ten minutes after mixing before the leu- 
cocytes are fully stained. Except for this delay, the only diffi- 
culty of this solution is that it is rather difficult to clean the 
pipette after using it. If the white cells are counted with an- 
other pipette the staining fluid can be as well dispensed with. 

Into a bottle of one of these solutions, ready at the bedside, 
the point of the pipette is to be plunged as soon as the blood 



12 



CLINICAL BLOOD EXAMINATION. 



has been drawn up to tlie point 0.5 and the outside of the pipette 
wiped clean of blood. Suction is then exerted through the 
rubber tube the instant the point of the pipette is below the sur- 
face of the diluting solution. This suction is continued until 
the diluted blood has filled the bulb of the pipette and gone 
past it up to the point marked 101. It is not difficult to stop 
at this point, provided the pipette is i)erfecth' clean and drv 
inside. Otherwise it is impossible. Should any mishap oc- 
cur at this point, the whole process must be begun over again 
after carefully cleaning and dry ing the pipette. If no acci- 
dent happens and the mixture is sucked up to and not past the 
mark 101, w^e have diluted the blood with two hundred times 
its bulk of neutral solution. If, instead of drawing the blood 
up to the mark 0.5 we draw it as far as the point marked 
1, and then dilute as above described, the mixture will be 
1 to 100. Some observers habitually use this dilution. The 
objections to it are : (1) That if the blood is accidentally drawn 
up too far {i.e., past the mark 1) we cannot draw it down again 
but must painfully clean and dry out the pipette (see below, 
p. 16) and repeat the process. (2) If the blood contain ap- 
proximately the normal number of corpuscles, they will be so 
crowded when adjusted on the ruled surface of the disc A that 
it is more difficult to count them. If we use another pipette for 
the white corpuscles the dilution of 1 : 100 has no advantage to 
counterbalance these drawbacks. 

While sucking in the diluting solution, it is well to roll 
the pipette on the long axis with the fingers of the hand which 
holds it in the diluting fluid. This mixes the blood instantly 
and prevents any of it from floating on the toj) of the solution 
and thereby coming m]) undiluted into the narrow portion above 
the bulb of the pipette, where it might possibly escape thor- 
ough mixing.* 

Next we thoroughly mix the blood and diluting fluid by 
shaking and rolling the pipette, its ends being closed by the 
fingers. The little glass ball within the bulb helps this process 
materially. A minute's brisk rolling and shaking is as good as 
five minutes', as I have convinced myself by many experiments, 
and the distribution of the corpuscles throughout the mixture is 

* Care must be taken that no saliva finds its way through the rubber 
tube and into the pipette. Never blow through the rubber tube. 



COUNTING THE CORPUSCLES. 



13 



very even, provided there is no delay in proceeding to the next 
step, viz. : 

(c) Adjusting a Drop of Diluted Blood in the Gountiyig Chamber, 
— Remove the rubber tube from the pipette and blow out the por- 
tion of diluting solution which last entered the pipette, and wdiich 
consequently has not been thoroughly mixed with the blood in 
the bulb. Five or six drops should be blown out before any is 
used for examination. Next put upon the surface of the counter 
(A, Fig. 3) a drop of such size that when the cover-glass (B) 



Fig. 3.— Thoma-Zeiss Counting Slide. A, Ruled disc ; B, cover-glass ; C, moat. 



is let down over it the whole of the disc A is covered with the 
drop without any being spilled into the "moat" (C) around it. 
Just how large such a drop should be can only be learned by 
practice. It is not literally necessary that exactlj^ the whole 
disc A should be covered, provided nine-tenths of it is covered, 
but any spilling over into the "moat" (C) entails serious error. 

After the cover-glass has been let down upon the drop, we 
should be able (provided the whole instrument is clean) to see 
concentric rainbow rings between the cover-glass and the body 
of the instrument. These are known as Newton's rings. A 
little pressure with a needle on the cover-glass will often bring 
them out if they do not at once appear, but they must remain 
visible after the pressure is taken off. Otherwise we know that 
there must be some dirt or dust under the cover-glass prevent- 
ing its settling exactly into position, and this will cause error in 
the count, though not a very considerable error in most cases. 
(To see Newton's rings we should get our eyes near to the level 
of the counting chamber so that the light from window or lamp 
is reflected from the surface of the cover-glass.) 

If the above conditions are not all fulfilled the instrument 
should be washed and another drop tried, after shaking the 
pipette and blowing out a few drops as before. 

The cover-glass must be let down as soon as possible after 




B 



'A 



C 



14 



CLINICAL BLOOD EXAMINATION. 



the drop lias been put on the disc A, and before the corpuscles 
have time to settle. It is best to let it down with, a needle as in 
monnting microscopic specimens. 

Coitnting. 

(d) After waiting two or three minutes so that the corpuscles 
may settle thoroughly upon the space ruled off on the disc A, 

A 




Fig. 4.— Thoma-Zeiss Counting Slide. A, Ruled disc. 



the counting is begun, using x)referably an objective 5 of Leitz 
or Jy of Zeiss and a No. 1 or 2 eyepiece. 

The ruled space on the surface of the counter (A, Fig. 4). 
is di^dded into four hundred squares, every group of sixteen 
squares being enclosed in double lines to make it easier to know 
how many squares we have counted (see Fig. 5). Including 
the squares with double lines we have a group containing thirty- 
six small squares, a group convenient to count at one time as it 
just about fills the field of the objective Leitz No. 5, or Zeiss D 
with a Xo. 2 eyepiece. 

To avoid considerable error we should count the corpuscles 
in five fields of thirty-six squares each, such as is shown in Fig. 
5, taking the fields in various parts of the whole ruled si)ace. 
The instrument should then be washed and the whole process 
repeated with a second droj). If the count of the second drop 
differs widely from that of the first, a third drop should be 
counted and the average taken of those two which are most 
nearly alike. Thus at least three hundred and sixty small 
squares should be counted ; with such a number the error is not 



COUNTING THE CORPUSCLES. 



15 



over three per cent for practised observers.* In normal blood 
this means counting about 2,160 corpuscles, as six or seven to a 
small square is about the normal average when we are using a 
dilution of 1 : 200 such as has been described (twelve to fourteen 
cells per square in a dilution of 1 : 100) . 

Among the difficulties encountered in counting is the pres- 
ence of a few corpuscles on or touching one or more of the lines 
hounding the space to 
be counted. Shall we 
count these out or in? 

In counting, for in- 
stance, a field like that 
in Fig. 5, what are we 
io do with the cells 
which sit astride the 
lines AA, BB, etc. ? 

To get round this 
difficulty, it is best to 
make it a rule to count 
in all the corpuscles on 
or touching some two of 
the boundary lines (e.g., 

AA and BB) and to Fig. 5.— Field of Thirty-six Squares on Ruled Disc of 
iake no notice of anv Thoma-Zeiss Counter Covered with Normal Blood 
" Diluted Two Hundred Times. 

€ell on or touching the 

lines CC and DD. In this way the exclusions just balance the 
inclusions. Of course all cells within these outer boundary 
lines are to be counted whatever their position. 

Beyond this the details must be settled by each man for him- 
self. My own habit is to count through the squares in the order 
indicated by the track of the serpentine arrow in the accompany- 
ing Fig. 6, and to count by twos or threes. 

A movable stage makes the counting easier, especially for be- 
ginners. Either natural or artificial light may be used with a 
small aperture diaphragm, and if the instruments are clean and 
the diluting solution fresh and free from sediment, f there is no 

* See Reinert's "Zahlung der Blutkorperchen," Leipzig, 1891, p. 48 et 
seq. 

\ Most diluting solutions precipitate or accumulate spores, and need to 
be frequently renewed. 



0° 

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16 



CLINICAL BLOOD EXAMINATION. 



difficulty in deciding how many cells each square contains, and 
no extraneous fragments to be excluded. We must distinguish 
the white corpuscles from the red, not by their size but by their 
stain if Toisson's solution is used, otherwise by their peculiar 
shining look when the lens is drawn up so as to put the red 
cells slightly out of focus. The blood plates are not noticeable 
and lead to no errors. 

When the number of corimscles in 360 squares has been 

counted the number is 
divided by 360 and multi- 
plied by 800,000 {i.e., by 
200 to make up for dilu- 
tion and then by 4,000 
because each square is 
equivalent to ^-q-q of a 
cubic millimetre), which 
gives us the number of 
corpuscles per cubic mil- 
limetre. 

These figures need not 
be committed to memory, 
for we have marked on 
the instruments used all 
the data necessary for the 
calculation, i.e., the dilu- 
tion figures on the pipette 
and the area and depth of a single square on the counting slide. 

(e) The importance of cleaning the pipette as soon as the 
counting is done is so great that it should be reckoned as one of 
the regular steps on every count. First water, then alcohol, and 
lastly ether must be sucked into the pipette and brought into 
contact with every part of the bulb and tube. After this air 
must be sucked or pumped through the tube until it is per- 
fectly dry and the glass ball will roll about freely in the bulb 
without sticking anywhere. 

These precautions take but two or three minutes, and if they 
are omitted and the blood dries in the pipette, it may take 
several hours' work to get it clean. Further, if it is not thor- 
oughly^ dried after cleaning, the mixing of the blood when it is 
used next cannot be done accurately. 































































m 


m 














r 








- 


7 












































) 






































f 

V 






























-< 



























































Fig. 6.— The Arrow Indicates the Order in which the 
Squares are Counted. 



COUNTING THE CORPUSCLES. 



17 



The first three steps of the above process {i.e., the obtaiuing, 
diluting, aud mixing of the blood) must be done as swiftly as is 
compatible with accuracy, but when once the blood is mixed in 
the pipette it can be kept there indefinitely and counted at 
leisure. None of the corpuscles are destroyed or lost, and if the 
bulb is thoroughly rolled and shaken up whenever we are ready 
to count the blood, no error results from keeping it twenty-four 
hours or more in the pipette. 

It is not necessary, therefore, to carry a microscope to the 
patient's house or bedside; the pipette and the diluting solution 
are all that we need to take with us, and when the blood is 
mixed in the pipette, the latter's ends can be closed with a 
rubber band and the blood carried home and counted at leisure. 
The pipette should be kept approximately horizontal during the 
transit. 

Counting the White Cobpuscles. 

To make a reasonably accurate count of white corpuscles, 
using the " red counter" and the dilution of 1 : 100 or 1 : 200, we 
need to count an immense number of squares, far more than was 
necessary in estimating the red cells — in fact, at least ten times 
the whole ruled space. It is therefore far more convenient and 
simple to use the " white counter" or large-bore pipette with a 
diluting solution which renders the red cells invisible and leaves 
only the white to be counted. Such a solution is the one-third 
of one-per-cent. solution of glacial acetic acid in water. With 
this the white corpuscles stand out very clearly and the red can 
barely be seen at all. The technique is the same as that already 
described, with the following exceptions : 

1. The drop of blood needed is nearly three times as large, 
as that used in the "red counter;" it is about as big as can be, 
made to stay on the ear without rolling off. 

2. The bore of the tube being large, it fills and empties, 
more readily. Hence our suction must be gentler,, and it is 
rather harder to stop exactly at the mark 11. For the same 
reason the diluted blood will run out of the pipette if the latter 
is not kept nearly horizontal, and the bottle of diluting solution 
should accordingly be tipped up as we plunge in the point of 
the pipette, so that the latter is depressed as little and for as; 
short a time as possible before suction begins, 

2 



18 



CLINICAL BLOOD EXAMINATION. 



3. Instead of counting separate fields of thirty-six squares 
each, we should count the whole ruled space and then repeat 
the process with a second drop. This takes never over fifteen 
minutes, often not over five, and is very accurate. 

The advantages of this pipette are obvious. The only draw- 
backs are its expense and the need of a somewhat deeper and 
more painful puncture to get blood enough for it. The tech- 
nique is not at all difficult. 

Counting Both Bed and White Cells With the Same Bipette. 

We may avoid buying both large-bore and small-bore pipettes 
in one of the following ways : 

1. We can count both red and white corpuscles with the " red 
counter. " 

2. We can count both red and white corpuscles with the 
"white counter." 

The reason why we cannot use the "red counter" for count- 
ing white cells, unless modified in some way, is that in the 
whole ruled surface of the counting chamber not more than three 
or four white corpuscles are to be found in normal blood when 
diluted two hundred times. If w^e dilute less, we cannot see the 
cells distinctly because they are so crowded. If we find, say, 
three white corpuscles as the number to be used as a basis in 
calculating the number of white cells in a cubic millimetre, the 
chance of error is very great, the multiplier being so large 
v(2,000) and the multiplicand so small (3). 

To get over this difficulty we may utilize the cells spread 
over the disc of the counting chamber outside the ruled space in 
one of the following ways : 

(a) By measuring the field of the objective used. The writer's 
objective, No. 5 of Leitz, has a field of very nearly one-quar- 
ter of a square millimetre or one-quarter of the whole ruled 
space. Four fields of this lens, taken anywhere outside the 
ruled space, therefore, contain the same number of cells as will 
cover the whole four hundred small ruled squares, and when 
we have counted the white cells in a series of four fields of 
this lens, we have accomplished as much as if we have put a 
fresh drop upon the counting chamber and counted all the 
ruled squares over again; the latter process is tedious, the 
former very quick. Thus it is my practice in some cases to 



COUNTING THE CORPUSCLES. 



19 



proceed as follows (see Fig. 7) : Supposing the large circle 
CCCC to represent tlie surface of the small disc (A, Fig. 3.) 
in the centre of the counting chamber, and AAAA the ruled 
squares in the mid- 
dle of this disc, four 
microscopic fields 
are taken in the di- 
rection away from 
the centre indicated 
by circles and ar- 
rows in the figure. 
Starting, say, to the 
right of the ruled 
squares with the 
left edge of the mi- 
croscopic field just 
touching the outer 
boundary line of the 
squares, count all 
the white cells to be 
seen in the field. 

Then move along to the right till the corpuscles which were on 
the extreme right of the first field have gone out of sight to the 
left. Your field is then in the position of the circle marked 
2 (Fig. 7). Count all the white cells in this field and so on 

for four fields. With my objective, four 
such fields are almost exactly equal to 
the whole ruled space AAAA. With 
other objectives of course the number of 
fields is different. 

When we have counted four fields 
in each of the four directions indicated 
by the arrows we have covered as much 
ground as if we have put four succes- 
sive drops on the slide after the first 
one and counted all the ruled squares 
in each, and we have saved much time and labor. 

(h) Another and better method of attaining this same end, in- 
vented, I think, by Dr. Franklin White, of Boston, is as follows : 
Cut out of black cardboard a piece of the shape shown in Fig. 





Fig. 8. 



20 



CLINICAL BLOOD EXAMINATION. 



8 and of sucli a size tliat it will fit into the tube of the eye- 
piece — the square aperture allowing a space of just one-quarter 
of a millimetre (one hundred of the ruled squares) to be seen 
through it v/ith a given objective (sa}' Leitz No, 5). Four 
fields as seen through such an aperture can then be counted 
in various parts of the slide outside the ruled space as ex- 
plained above. 

(c) For any one living where "microscopic ruling on glass can 
be done at a moderate cost, by far the best way is to have the 
rest of the disc A (Fig. 4) ruled off in large squares of just a 
square millimetre each. I have not been able to hear of an}' one 
in America who could do such work at a moderate expense. 

2. We may use the " white counter" for red cori)uscles in the 
following way : Suck up blood only to the first mark up from 
the point (i.e., one-fifth of the usual distance) and then Gowers' 
or Toisson's solution up to the mark 11. This gives a dilution 
of 1 : 100, and in anaemic cases, in which the cells are not very 
numerous, answers well. The same pipette can then be care- 
fully cleaned and used for counting white cells with the acetic 
acid one- third per cent, and a dilution of 1 : 10 or 1 : 20, 

Whatever method of counting white corpuscles is adopted, 
we ought to have at least one hundred corpuscles actually 
counted to use as the multiplicand of our computation. A single 
drop from the white counter with a dilution of 1 : 10 gives us 
normally about seventy white corpuscles in the four hundred 
ruled spaces, and by repeating the process with a second drop 
the result may be made reasonably accurate. This was the 
method adopted by Rieder"^ in the immense number of counts 
made by him. 

* " Beitrage zur Kenntniss der Leucocytosis, " Leipzig, 1892 (Vogel) 



CHAPTER III. 



CENTRIFUGALIZING THE BLOOD— HEMOGLOBIN ESTIMATION 
—SPECIFIC GRAVITY— STAINED SPECIMENS— BACTERIO- 
LOGICAL EXAMINATIONS. 

The Hematocrit. 

The lisematocrit of Hedin, though a comparatively new in- 
strument, has undergone considerable modification and improve- 
ment in the last few years and as remodelled and improved by 
Judson Daland is now coming into use in this country. Its 
direct and obvious object is simply to ascertain the relative 
volume or mass of the corpuscles and of the plasma in a drop of 
blood; but the hope of its advocates has usually been that it 
would supplant entirely or mostly the long, tedious, and eye- 
destroying process of counting with the Thoma-Zeiss instrument. 
Whereas the latter needs sometimes an hour's hard work and 
eye strain to make an accurate count of red cells, with Daland's 
centrifugal machine one can get the result in five minutes with- 
out any strain on the eyes. 

Daland maintains the superior accuracy of his instrument in 
most cases as a further advantage of its use. The estimation 
of corpuscles depends on the length of the column of corpuscles 
packed down by centrifugal force at the end of a capillary tube 
filled with blood and whirled with great rapidity in a horizontal 
plane. The more corpuscles the longer the column. 

Wherever there is much variation in the shape or size of the 
cells, as in many forms of anaemia, leukaemia, etc., the hsematocrit 
is evidently inaccurate, inasmuch as the misshapen, under- or 
oversized corpuscle will pack down differently from the normal 
cells, three million undersized cells making a shorter column in 
the tube than three million healthy ones. This is recognized 
by the advocates of the instrument, which is accordingly recom- 
mended only in those cases in which we know that there are no 
considerable variations in the size or shape of the red cells. 
These are usually cases in which no very great anaemia is pres- 



22 



CLINICAL BLOOD EXAMINATION. 



ent and in wliicli consequenth' the labor of counting the large 
number of corpuscles is greatest. It seems, therefore, as if the 
hsematocrit might relieve us of the most irksome part of blood- 
counting without loss of accurac}'. 

Against this there is to be said that we do not as jet 
know how far the elasticity and compressibility of otherwise 
healthy corpuscles may vary, and how far such a variation may 
invalidate the standard of tight packing established from other 
cases. Further, there is known to be a certain amount of varia- 
tion in the size and volume of a healthy person's corpuscles, both 
between nations and between members of one nation, and it is 
yet to be sho^ni whether this variation is sufficient to make the 
result of the haematocrit liable to a greater error than those of 




Fig. 9.— Capillary Tube of Hasmatocrit with Rubber Attached. 



the Thoma-Zeiss instrument. There is no doubt that the lat- 
ter is a slower, more tedious instrument ; the question is still 
open whether or not it is the more accurate. Daland reports 
wide variations between his counts and those of his colleague 
and between different counts by one observer at different times, 
using the Thoma-Zeiss instrument, while with the hsematocrit 
the variations are but slight. 

In testing these results I have made parallel counts of a pa- 
tient's blood with several of the house physicians at the Massa- 
chusetts General Hospital during the last two years and our 
differences have never exceeded the limit of error laid down by 
Reinert — namely, two per cent. I think Daland must have 
been unfortunate in his results. 

If, then, the error of the Thoma-Zeiss instrument is, as I 
believe, not over two per cent under ordinary circumstances and 
with correct technique, it does not seem likely that the hsema- 
tocrit is a more accurate as well as a simpler and quicker in- 
strument. 

To use the Daland hsematocrit we prick the ear as usual and 
with the help of a bit of rubber tube attached to one end of the 



CENTRIFUGALIZING THE BLOOD. 



23 



capillary tube (Fig. 9) suck in enough blood to fill it entirely. 
Usually we draw in more than enough and it enters the rubber 
tube as well, but this is no harm. It is nearly impossible to fill 
the glass tube exactly and no more, inasmuch as the proximal 
end of it is hidden inside the rubber tube. The commonest 




Fig. 10.— Daland's Hsematocrit. Two capillary tubes in place on the horizontal whirling 
beam. The instrument is to be fastened to the edge of some solid and bulky piece of 
furniture by means of the thrumb-screw seen at the bottom of the cut. If not very 
tightly secured, it will work loose when the handle is revolved rapidly. 

mistake at this point is incomplete filling of the capillary tubcj^ 
as a very large drop is needed to do it. 

As soon as it is full, put the finger (greased with vaseline) 



24 



CLINICAL BLOOD EXAMINATION. 



tightly over the free end of the glass tube and then, hut not till 
then, draw off the rubber tube and adjust the glass as quickly 
as possible in the place prepared for it on one of the horizontal 
arms of the whirling machine (Fig. 10). A similar tube (empty) 
should be put on the other arm of the crosspiece to make the 
balance true. We must be quick about this, else the blood will 
coagulate. The handle of the instrument is then revolved at 
least seventy times a minute for two minutes, at the end of 
which time (sometimes less) the column of blood cells is packed 
so tight that no further whirling has any effect on its length. 
Great care should be taken that the horizontal beam is securely 
attached to the main part of the instrument, as it is capable 
of doing serious damage should it come off while whirling 
nine thousand revolutions a minute, which is the rate usually 
attained. 

It is well to put a little vaseline on the point where the blunt 
end of the tube rests (a. Fig. 10) to prevent any of the blood 
sticking there when we come to take the tube out and read it. 

The capillary tube is marked off into one hundred equal 
divisions and provided with a magnifier like that on clinical 
thermometers. Laid on a piece of white paper it is easy to read 
•off the number of divisions occuj)ied by the blood column, al- 
though the end of it is often frayed or bevelled in a way that 
precludes great accuracy. In normal blood the white corpuscles 
hardly show at all in the tube. They accumulate at the free 
end of the column of red cells, but unless a leucocytosis is 
present their presence is indicated, if at all, only by a slight 
grayish blur at the end of the red column and cannot be accu- 
rately measured. This blur is another difficulty in the way of 
deciding precisely where the end of the red-cell column is. 

To estimate the number of red corpuscles from the length of 
the column, we call each degree of the scale on the tube 100,000 
cells, or a little more. Thus if the blood column in the tube 
ends at about the mark 50 we consider that the blood has rather 
more than 5,000,000 red corpuscles per cubic millimetre. So 
far all observers agree on the figures, but as to just how much 
more or less than 100,000 each degree on the scale is worth there 
is some variation between different observers . Daland, * in a long 
series of comparative observations of making blood counts and 
* University Med. Mag. , November, 1891. 



HEMOGLOBIN ESTIMATION. 



25 



hfematocrit estimations on tlie same case, conclude that each 
degree of the scale on the capillary tube corresponds to 99,390 
corpuscles. 

The writer in a series of forty observations on healthy 
persons, in each of which a count of corpuscles with the Thoma- 
Zeiss instrument and a volumetric estimation with Daland's 
hsematocrit was made, found the value of one degree on the glass 
scale to vary between 105,000 and 123,000 red corpuscles, the 
average being 112,000. 

It certainly seems a 'priori as if variations in the specific 
gravity of the corpuscles or in the properties of the plasma 
might make a considerable difference in the number of revolu- 
tions needed to reduce the column of corpuscles to its smallest 
size. 

So far as I can learn, the use of this instrument in Europe 
has been chiefly for the direct information it affords as to the 
volume of the red cells and the amount of respiratory surface in 
the blood, rather than for the indirect information it may give 
us as to the number of the red cells. It does not seem as yet to 
be supplanting the Thoma-Zeiss counter. 

Its bulk and the noise it makes must for the present, I think, 
prevent its extensive use outside of hospitals. The noise it 
makes is a very loud and disagreeable one, and will deter many 
from using it in private practice. 

HAEMOGLOBIN ESTIMATION. 

The instrument most used both here and in Europe is that 
of V. Eleischl. In France Hay em rules supreme in the matter 
of instruments, as in everything else concerning the blood, and 
in England Gowers' apparatus is used to a certain extent. Only 
the V. Eleischl instrument will be described here. The prin- 
ciple of its use is that of directly comparing the tint of the blood 
with various parts of a strip of colored glass {" goldpurpur') 
whose color shades gradually from a deep red at one end to 
clear glass at the other. The glass and the blood are brought 
before the eye side by side and a direct color judgment is 
attempted. 



26 



CLINICAL BLOOD EXAMINATION. 



Use of V. FleiscJiVs Hcemometer. 

(a) To use the instrument fill one side of the metallic cell (a. 
Fig. 12) about one-quarter full of distilled water and carry it 
to the bedside, together with the little capillary pipette (B, Fig. 

11) and the needle for puncturing. The capillary pipette 
must be scrupulously cleaned and dried before 
use. This is best done by drawing a needle 
and thread (the latter wet with alcohol and 
ether) through the eye of the capillary tube. 
When the drop of blood is flowing freely from 
the eiir, put the end of ^ the little pipette hori- 
zontally into the side of the drop, which will 
at once fill the tube by capillary attraction if 
the latter is clean and dry. Carefully but 
quickly wipe away any blood that may be on 
the outside of the pipette, and make sure that 
the blood in it is just flush with the surface 
at each end and does not present a concave 
or convex surface. Then put it into the water 

Fig. 11.—"^, Colored Contained in one of tlie partitions of the metal- 
giass; B, capillary i[q ^ell and rattle it quickly back and forth, 
so that the water may be forced in first at 
one end and then at the other. So far in the process we must 
work very quick to prevent coagulation which in some cases 
takes place very rapidly. 

(h) After this the cell with the capillary tube still immersed 
in it may be put in place on the body of the instrument (see Fig. 

12) and carried to a room or closet where daylight can be ex- 
cluded and artificial light used to read the instrument by. Then 
the expulsion of the blood from the capillary tube may be com- 
pleted by forcing a few drops of water from a medicine dropper 
through the capillary pipette and into the compartment where 
the mixing has been begun. Using the metal handle of the 
pipette as a stirrer, mix very thoroughly the blood and water 
in every part of the compartment, looking after the corners 
especially. Then using a medicine dropper, fill both com- 
partments of the cell to the brim with distilled water, taking 
care that neither overflows into the other, and adjust the com- 




HEMOGLOBIN ESTIMATION. 



2? 



partment containing the clear water so that it comes over the 
slip of colored glass, while through the compartment containing 
the blood light thrown ui)ward by the reflector below passes 
directly to the eye. Turn the thumb screw (see Fig. 12, T) back 
and forth until the color of the glass is the same as that of the 
blood, and read off the number on the scale which corresponds 



Fig. 12.— v. FleischPs Haemometer. a. Partition into which blood is put ; a', partition 
into which water is put ; (?, mixing cell ; K, K, colored glass slip (see Fig. 11, A) ; 
P, P, metal frame on which scale is marked ; P, S, reflector ; T, screw which moves 
the frame, P, P. 

to that color. This gives the percentage of haemoglobin, 
100 being the color of normal blood for men and 80-90 for 
women. 

(c) Matching the colors is not at all easy at best, but may be 
somewhat aided by observing the following precautions : 

1. Do not stand {or sit) facing the light, but sideivays {i.e., at 
A or B, never at C, Fig. 13) . For we wish to avoid that the 
image of one compartment should come on the upper half of the 
retina and of the other compartment on the lower half, inasmuch 
as the upper half of the retina is less sensitive to light than the 
lower and so a less accurate judge of color. By sitting as in 
Fig. 13, A or B, we get the compartments whose colors we 
are to match, on the right and left halves of the retina, which 
are equally sensitive in most persons. 




28 



CLINICAL. BLOOD EXAMINATION. 




B 



2. Use as little light as possible, and always less light for a 
blood having a low haemoglobin percentage than for one nearer 
the normal. Slight color distinctions are abolished if there is 
any more light than is necessary for simple illumination ; too 

much light dazzles us 
slightly and so makes us 
less sensitive in color dis- 
crimination. 

3. Roll up a piece of 
paper {preferahly black) into 
a tube of such size that it 
will fit over the metallic 
cell (D, Fig. 13) and rest on 
the platform of the instru- 
ment. Looking through this 
with one 'eye we can judge 
more accurately than with- 
out it. Keep the other eye 
closed. 

4. Use Jirst one eye and 
then the other, and never 

look more than a few seconds cd a time, as the eye very quickly 
gets sufficietitly fatigued to lose its finer sensibilit}'. Hence the 
impression of a first glance is better than a long look. 

5. 31ove the thumb sa'eiv icith short, quick turns rather than 
slowly and gradually, for sudden color changes affect the retina 
more than gradual ones. Suppose, for example, we have got as 
far as to decide that the tint of the diluted blood corresponds to 
that of glass someivhere between the numbers 40 and 60 on the 
scale. Move the screAV suddenly from 40 to 55 ; the shock of 
the change will probably convince 3^ou that the blood color is 
lighter than 55. Therefore start this time at 55 and move it 
suddenly to, say, 45, which may show that 45 is too light. 
Thus by a series of quick movements of the screw getting 
shorter and shorter each time (with frequent rests for the eyes) 
we can probably get it down to a matter of doubt between, say, 
42 and 45. Beyond that few persons can go and many can never 
learn to read without an error of five to ten per cent. 



Fig. 13.— Light; A and 5, right positions for 
observer ; C, wrong position for observer ; Z), 
cell in place. 



SPECIFIC GRAVITY. 



29 



Necessary Errors. 

So far as I can see, a certain amount of error is absolutely 
necessary, inasmuch as the bit of colored glass to be seen at any 
one time through the aperture of the instrument is not (like the 
blood) all of one tint, but includes a variation of twenty per cent in 
color, i.e., if the glass appearing at one end of the aperture is 
opposite 50 on the scale, that seen at the other end of the aper- 
ture will either be at 30 or at 70. We have, therefore, to pick out 
as well as we can the color of the centre of the bit of glass show- 
ing through the cell and compare the color at that point with 
the color which is evenh' distributed throughout the whole of 
the blood-and-water compartment. This is of course, strictly 
speaking, impossible. We can no more get hold of and sepa- 
rate out the color of that central iDoint than we can seize and hold 
fast the present moment. It eludes our grasp. 

Many persons are not sensitive enough to colors to attain any 
reasonable degree of accuracy with the instrument, and there is 
moreover a very considerable difference between different instru- 
ments in respect to the color of the glass slip.* Finally the in- 
strument has been shown to be entirely unreliable for percent- 
ages of haemoglobin under 20. 

All these difficulties render the instrument an unsatisfactory 
one in many ways. Its bulk and expense are also considerable 
drawbacks. 

Is there no other way of getting at the information we desire? 
None of the other clinically available methods hitherto sug- 
gested are any more reliable than v. Fleischl's. But it seems to 
the writer that in the process next to be described, the specific- 
gravity estimation, we have a means of getting at the haemo- 
globin percentage indirectly, which may prove to be in many 
■ways superior to any available direct method. 

Estimating the Specific Gravity of the Blood. 

The simplest and most available method for clinical use is 
that of Hammerschlag, f a modification of Eoy'sJ method. 

* Old instruments read lower than those recently manufactured. 
fWien. klin. Wochenschrift, iii., 1,018, 1890. 
X Proceedings of Physiological Society, 1884. 



30 



CLINICAL BLOOD EXAMINATION. 



Chloroform is heavier tlian blood; benzol is lighter. Mix in a 
urinometer glass such quantities of the two that the specific 
gravity taken by an ordinary urinometer is about 1059, i. e. , that 
of normal blood. Puncture the ear, draw a drop of blood into 
the tube of a Thoma-Zeiss pipette, a small medicine dropper, or 
any other capillary tube, and blow it out again into the chloro- 
form-benzol mixture. The blood does not mix at all with these 
liquids but floats like a red bead. If it sinks to the bottom add 
chloroform, if it rises to the top add benzol, until finally the 
drop remains stationary in the body of the liquid, showing that 
its specific gravity is just that of the surrounding mixture. 
Then take the specific gravity of the liquid, as we do of urine, 
and you have the specific gravity of the drop that floated in it. 
The following precautions are needed : 

1. Have the inside of the urinometer glass perfectly dry and 
clean ; otherwise the drop of blood may cling to it and flatten 
out against it. 

2. It is usually well to have more than one drop of blood in 
the glass in case any mishap occurs with the first one. 

3. Add the chloroform and benzol a few drops at a time, and 
after each addition stir the whole mixture thoroughly with a 
glass rod. 

4. If we have reason to suppose the blood will be lighter 
than normal {i.e., if the haemoglobin is probably low, vide infra), 
it saves time to start with a lighter mixture of chloroform and 
benzol. 

5. Avoid having any air within the blood drop. This can 
generally be seen either in the capillary tube or after the drop 
is in the mixture. It is safer to take the middle portion of the 
blood drawn into the capillary tube, as both the first and the 
last portions of the column are more apt to have air in them. 

It is better to have a urinometer with a scale running as high 
as 1070, but this is not essential, for the clinically important 
specific gravities are loiv, not high. 

The importance of the specific gravity of the blood, as hinted 
above, is not so much for itself, but because it runs parallel to 
the percentage of haemoglobin and gives a figure fi^om which the 
latter can be computed. 

The specific gravity of the blood plasma varies very little 
(except in dropsy from any cause) , and in the corpuscles them- 



SPECIFIC GRAVITY. 



31 



selves the variable element is the haemoglobin.' Consequently 
in most non-dropsical patients the specific gravity of the whole 
blood varies as directly as the haemoglobin. 

Now, as it is far easier to take the specific gravity accurately 
than to use the v. Fleischl haemometer, and as the instruments 
needed are already in the jjossession of most physicians and 
the solutions not expensive, there are evidently great advantages 
in taking the haemoglobin in this indirect way. The chloroform- 
benzol mixture can be filtered and then used over again indefi- 
nitely, and the bulk and w^eight of the urinometer with its glass 
and the chloroform and benzol bottles, are far less than that of 
the V. Fleischl instrument. 

In dropsical cases we must still use the v. Fleischl instru- 
ment. In other conditions I do not see why it should not be 
supplanted by the cheaper, easier, more accurate, and equally 
quick method of calculating by specific gravity. To do this 
one of the following tables may be used. (I. is from Hammer- 
schlag, using the method above described ; II. is modified from 
Schmaltz, "Pathologie des Blutes," etc., Leipsic, 1896, using a 
direct weighing method.) Apparently a degree of specific grav- 
ity means much more at the top of the scale {i.e., 6.6 per cent) 
than at the bottom (If per cent). These tables are of course not 
accurate, and further research will be needed to make them so. 



Spec. Grav. 
1033-1035 : 
1035-1038 
1038-1040 : 
1040-1045 : 
1045-1048 : 
1048-1050 : 
1050-1053 : 
1053-1055 : 
1055-1057 : 
1057-1060 



I. 

Haemoglobin. 
25-30 per cent. 
30-35 
35-40 
40-45 
45-55 
55-65 
65-70 
70-75 
75-85 
85-95 



Spec. Gi-av. 


Haemoglobin. 


1030 = 


20 per cent. ± 


1035 = 


30 


1038 = 


35 


1041 = 


40 


1042.5 - 


45 


1045.5 = 


50 


1048 - 


55 


1049 = 


60 


1051 = 


65 


1052 : 


70 


1053.5 = 


75 


1056 = 


80 


1057.5 = 


90 


1059 = 


100 



Study of the Finer Structures of the Blood. 

The study of dried and stained specimens with the help of 
the aniline dyes gives us much of interest and importance in 

' Except in dropsy in which the corpuscles themselves may get water- 
soaked. 



32 



CLINICAL BLOOD EXAMINATION. 



regard to the blood. More can be told about a given case by 
the study of a dried and stained cover-glass specimen than by 
any other single method. 

Preparation of Cover- Glass Specimens. 

(a) Covers carefully cleaned with soap and water are ar- 
ranged at the bedside in such jjosition that we can quickly pick 
them up without touching their surfaces (see Fig. 1). The ear 
is punctured in the usual way, and one of the cover-glasses 
touched to the summit of the drop as soon as it emerges. This 
cover-glass is then let fall upon another 
in such a way that their corners do not 
coincide (Fig. 14). If the covers are 
clean the drop spreads at once over their 
whole surface ; as soon as it stops spread- 
ing, slide off the top one tuithout lifting 
them apart, but exactly in the plane of 
their surfaces. Have a gas or alcohol 
flame at hand and dry instantly if you 
want to get the very best specimens; 
but this is not at all necessary for most clinical purposes. 
The under cover-glass is alw^ays better spread than the upj)er. 

(h) These covers have now to be fixed either by heat or by 
half an hour's immersion in absolute alcohol and ether (equal 
parts). 

When we wish to study chiefly the changes in the red cells 
(as in stud^dng the malarial organism, nucleated red corpuscles, 
degenerative changes, etc.), the alcohol and ether method is 
preferable. But when, as in the majority of cases, it is the 
white cells in which our interest, centres, the use of heat is very 
greatly to be preferred. 

The method of fixation by alcohol and ether needs little com- 
ment, the cover-glasses being simply left in the mixture half 
an hour or as much longer as is convenient. Half an hour is 
enough. In most cases we use dry heat, which coagulates the 
albumin and prevents the haemoglobin from being washed away. 
The best way to do this is in a dry heat sterilizer at a tem- 
perature of 110-115° C, according to the stain used. The 
temperature must be gauged very accurately. If we cannot 
easily get access to such an instrument, we can manage very 




STAINING. 



33 



well with a strip of copxjer supported over a Bunsen burner or 
a small gas or oil stove. The copper plate should be about a 
foot long and two or three inches wide. Such a plate sup- 
ported on an iron tripod over a flame gets, after a few minutes, 
to have a fixed temperature at any given distance from the flame,^ 
the heat passing off at the end of the plate as fast as it comes, 
and so not accumulating. On this plate find the boiling point 
of water by dropping small drops of water on it, and put the 
cover-glasses at this point face, doicmcard. They maj- be left 
there for from fifteen minutes to as long as you please ; but with 
the stain which I have used, fifteen minutes' heating gives as 
good results as a longer period, and excellent specimens can 
often be made with five minutes' heating.^ After allowing the 
specimens to cool they are ready for staining. 

Staining. 

For all details of structure the Ehrlich tricolor mixture or 
one of the numerous modifications of it is most convenient. 
The most useful and easily obtained of these is made by mixing : 

Ehrlich-Biondi powder,'^ gr. xv. 

Alcohol (absolute) , 1 c. c. 

Distilled water, 6 " 

The Ehrlich-Biondi powder is best obtained from G. Grubler 
& Co., Leipsic, and the same firm supplies leading dealers in 
this country with the mixture made up ready for use. Several 
samples of this which I have tested have given excellent results. 

Others prefer to make up the tricolor mixture for themselves 
according to Ehrlich 's directions. His latest formula is as fol- 



lows : 

Saturated watery solution of orange G, . 120-135 c.c. 

" " " " acid fuchsin, . 80-165 " 

" '* " " methyl green, . 125 " 

Glycerin, 100 " 

Absolute alcohol, = 200 " 

Distilled water, 300 



^ If we are in a great hurry, the most important points can generally 
be made out even if the specimen is simply held in the finger over the 
flame as hot as can be borne for thirty or forty seconds, and stained the 
same length of time. 

2 Late specimens of this powder have been unsatisfactory. An absol- 
utely reliable triple-stain from Ehrlich 's latest formula can be had of 
Walter Dodd, apothecary to the Massachusetts General Hospital. A 65- 
cent bottle will stain several thousand specimens. 
3 



CLINICAL BLOOD EXAMIXATIOX. 



I have but little personal experience witli this mixture, hav- 
ing generally used the Ehrlich-Biondi stain according to the tii'st 
receipt given above. 

The staining process is remarkably simple. The stain is 
simply spread over the surface of the cover-glass specimen with 
a glass rod and washed off again with water after from one to 
five minutes. The exact time of staining depends {o) on the 
length of time that the specimen has been heated, and {h) on the 
particular specimen of stain. The aniline colors vary so much 
that it is rare to get two mixtures that stain just alike, even 
though made upon the same formula. 

In a general way the shorter the time we heat the shorter we 
stain. Thus a specimen hastily i^repared by holding it in the 
fingers over a flame, needs only thirty to sixty seconds staining. 
Those heated an hour need three to five minutes. 

Each observer must work the details out for himself after 
learning from some " show specim^"' how a good stain looks. 

After staining and washing in water, the covers are dried be- 
tween layers of filter paper and mounted in Canada balsam, 
ready for examination with the one-twelfth oil-immersion lens, 
with wide open dia]3hragm. 

Diffe rerdial Counting. 

"The only procedure in the microscopic examination of such 
specimens which needs any description is that of making the so- 
called "differential count" of the leucocytes [i.e., determining 
what percentage of the leucocytes present belongs to each of the 
sub-varieties as described on pp. 48-57). To do this accurately 
we should examine at least one thousand leucocytes — the exami- 
nation being simply the classification of them under their diff^er- 
ent sub- varieties. A movable stage is very convenient though 
not essential for this xjurpose. T\'ith such a stage the technique 
is simply to start with the lens in, say, the vij[>tr left-liand coYYiQ.v 
of the blood film and, by turning the screw of the mechanical 
stage, move the prei3aration slowly past the eye until the iqrper 
righf-li/iiid coTHieT is reached. During this process as the cells 
appear in the field they are checked off and put down under one 
or another heading. Then move the stage so that the lens is 
just one field's diameter nearer the riql>f-]iriyir] Imrfr corner of 
the preparation, and go back again from right to left, following 



BACTERIOLOGICAL EXAMINATION. 



35 



the serpentine track indicated above in Fig. 6. To move the 
lens just one field's diameter we have only to fix the eye on a cell 
at the extreme edge of the field and then move the stage till that 
cell disappears out of sight on the opposite side of the field. 
Thus we avoid any chance of counting the same cells twice, and 
yet are sure not to miss seeing any. 

As we go back and., forth in this way, we notice chiefly the 
white cells of course, but yet keep our eyes open for any unusual 
appearances in the red cells. Usually these move by in a 
monotonous stream, one looking much like another, but in 
pathological blood we must always be on the lookout for nu- 
cleated red cells, degenerative changes, and variations in size 
and shape. In malarial cases of course our scrutiny is directed 
chiefly upon the red cells. 

If we have not the help of a movable stage we try to do the 
same thing moving the slide with the fingers. With moderate 
care there is no danger of counting the same cells twice, but 
we cannot help missing a good many altogether, so that although 
accurate the process takes longer. 

AYhen leucocytosis is present, at least one thousand leuco- 
cytes can be found in a single well-spread seven-eighth-inch cover- 
glass specimen. In normal blood we may need to go through 
two to three covers. 

Bacteriological Exa^iinatiox. 

Blood obtained by the ordinary method of puncture is rarely 
fit for bacteriological examination. The following is the better 
way : 

Sterilize the skin over the flexor surface of the bend of the 
elbow, and wash off thoroughly the agents used for sterilization 
with boiled water or boiled normal salt solution. Have an as- 
sistant grasp the upper arm so as to prevent the venous return 
and distend the large veins at the elbow. Into the most promi- 
nent of these iDlunge a sterilized hollow needle connected with 
the bulb of a sterilized syringe. All traces of antiseptics must 
be carefully washed out of the needle and the syringe bulb be- 
fore using. 

When the needle penetrates the wall of the vein the blood 
usuaUj' begins to flow into the bulb of the syringe, and this is 



36 



CLINICAL BLOOD EXAMINATION. 



hastened by gently withdrawing the piston until 1-2 c.c. of blood 
are in the bulb. Then withdraw the needle, press a pad of 
sterilized gauze over the wound, and expel the blood before it 
coagulates into a blood-serum culture tube so that it shall run 
down over the whole surface of the "slant" and collect a little at 
the bottom. The tubes are then put at once into the thermostat. 

In examining for the gonococcus the blood is to be mixed 
with equal parts of agar-agar (previously melted down so as to 
be mixable but not hot enough to kill the organisms) , and then 
plated. 

The further examination of cultures falls outside the scope of 
this book. 

In the above procedure the only difficulties are: 1. Some- 
times it is hard to find a vein and to get the needle into it. 
2. Occasionally we get the needle entirely through the vessel 
into the tisuses on the other side. 

If the blood does not flow readily into the bulb one of these 
two mistakes is usually the cause, but occasionally in those 
whose vessels are Yery small or whose circulation is very feeble 
(as in the moribund) it is very hard to get the requisite amount 
of blood. Only practice helps us to avoid these difficulties. 

The procedure causes hardlj^ more pain than the use of an 
ordinary subcutaneous injection; the process of sterilization is 
usually more irksome to the patient than the puncture. 

Bleeding is trifling, and within twenty-four hours there is 
usually no trace of the puncture left. A sterilized dressing with 
moderate pressure should be applied. 

Other Methods of Blood Examination. 

It is perhaps worth while briefly- to meution some other 
methods of blood examination of which no account will be 
given. 

1. Determination of the alkalinity of the blood. No clinically 
available method has been devised and the accuracy of any 
method hitherto described has been doubted by good authorities 
(v. Noorden, v. Limbeck). 

2. Resistance of the red corpuscles to the infiuence of dis- 
tilled loater. As is well known, water breaks up red cells, but 
if" we add a certain amount of alkali, say NaCl, the cells re- 



OTHER METHODS. 



37 



main uninjured. The amount of NaCl which has to be added 
to prevent the destruction of red cells is from 0.44 to 0.48 per 
cent. Under certain pathological conditions it needs either 
more or less of the salt to keep the cells intact, i.e., they pos- 
sess an increased or diminished power of resistance against the 
destroying influences of distilled water. The degree of con- 
centration necessary to maintain red corpuscles intact is known 
as the isotonic coefficient of the blood as stated in terms of a 
given salt; 0.44-0.48 is thus the coefficient of normal blood cor- 
puscles in NaCl. 

Possibly this method of examining blood may in the future 
give us knowledge of clinical value. At present it is not clini- 
cally applicable. 

The resistance of the blood cells to the influence of elec- 
tricity, heat, and mechanical pressure has also been investigated 
in various conditions of health and disease. 

3. The rapidity of coagulation varies markedly in different 
diseases, but no reliable way of measuring it has yet been found. 

4. The amount of solids in a given quantity of blood can be 
determined by weighing a given amount of blood before and 
after six hours' drying at 65° C. Inasmuch as the haemoglobin 
percentage and the speciflc gra\dty run practically parallel with 
the amount of solids this method has no considerable clinical 
value. 



PART II. 



PHYSIOLOGY OF THE BLOOD. 



CHAPTEK IV. 

Only such portions of our knowledge of blood physiology 
will be entered upon here as are necessary for an understanding 
of the small group of pathological changes which can be profit- 
ably investigated by clinicians. This limits us for the present 
to the morpliology of the blood, its coloring matter, and its density 
under physiological conditions. 

Appeaeance of Fresh Normal Blood. 

A drop of normal blood spread between slide and cover-glass 
as directed on page 7 and examined immediately with a one- 
twelfth immersion lens, amazes us first of all by the entire ab- 
sence of an 3^ red color. All we see is a colorless liquid in which 
masses of very pale greenish-yellow discs are floating or lying. 

I. Red Cojyuscles. 

(a) If the blood is spread thickly the blood discs are often 
arranged in the /orm of rouleaux (Fig. 15). The entire absence 
of this tendency to rouleaux formation is pathological. It is to 
be avoided, of course, as far as possible, as it gives us only the 
thin edges of the corpuscles to look at and covers up much that 
we need to study. Thin spreading of the blood is therefore im- 
portant. 

(b) There is not much variation from the accurately round 
shape of each corpuscle in normal blood, except where one is 
indented by another. As they are moved about by the currents 
set in motion by the gradual drying up of the plasma and strike 
against each other, they bend, double up, or indent each other, 



PHYSIOLOGY OF THE BLOOD. 



39 



like bags of jelly, but yet always have a strong tendency to 
return elastically to their round outline when free from pres- 
sure. Thus a corpuscle passing through a narrow passage be- 
tween two leucocytes will be flattened out like a worm ; but as 
soon as it emerges on the other side, it will be as round as 
before. 

(c) The central hiconcavity of the cell, being thinner than the 
rim, is lighter colored. Just how much lighter should be learned 
by practice so that we may detect any abnormal 'pallor of the 
corpuscles due to lack of haemoglobin. Pallor is to be seen 
mostly in the centre of the cell, which in extreme cases seems 
almost transparent. This is not to be confounded with the 
highly refractile glistening white centres seen as a mark of 
necrosis as soon as the blood begins to dry up. A fuller de- 
scription of these appearances is given in the chapter on the 
malarial organisms, with some forms of which it may be con- 
founded. 

{d) Slight variations in size are present among normal red 
discs, and here again only practice can teach us where the normal 
limits end and the pathological begin. Cells may be (patho- 
logically) all undersized or all oversized, so that a standard of 
comparison is not always to be looked for in the preparation 
itself. 

(e) If we focus carefully on a single red cell we can usually 
make out a fine, wavy, so-called molecular motion in it. This is 
quite different from the active amoeboid movements observed 
in dying cells, and from the rapid dancing of malarial pig- 
ment. 

(/) The familiar appearance of spines all over the cells 
usually called " crenation' need not be described here (see Fig. 
18, p. 72). _ 

But it is the very earliest beginnings of crenation that lead 
to mistakes, as when only one projection has been developed 
and that points toward the eye, so that a bright spot in the cor- 
puscles is all we see. 

( g) Unless we disinfect the skin before puncturing we must 
be prepared to find in fresh preparations (a) oil drops ; (b) epi- 
thelium; (c) particles of "dirt;" (d) small colorless motile 
organisms about 1 /j- in diameter, which are not at all rare but 
whose nature is unknown to me. 



40 



CLINICAL BLOOD EXAMINATION. 



(h) We may make a rough estimate of the vumher of red cells 
present if we take care to si)read the droj) of the same thickness 
each time. The eye gets used to the ordinary look of a well- 
filled field of corpuscles and notices a look of thinness if any 
considerable anaemia is present. 

{i) The degenerative changes to be seen in normal blood after 
long exposure to the air, which can get in between slide and 
cover, are described in detail later on. In pathological blood 
we may find these as soon as the blood is drawn. 

//. White Cells. 

(a) The luhite or colorless corpuscles are but little different 
from the red in color, the latter being so nearly colorless. We 
first notice them either by their amoeboid movements, or because 
they are not moved by the plasma currents, but stand like a rock 
round the sides of which the current of red cells is broken. 
Thej^ are slightly larger in most instances than the red cells ; but 
this difference shows less in the fresh si^ecimens where the leu- 
cocyte keeps its spherical shape than in the dried and stained 
preparations, where it is usually somewhat flattened. Their 
shape is very irregular and their edges often look tattered. 

In some leucocytes the amoeboid motions are entirely absent. 
These are the smallest sizes, and in them a single nucleus filling 
most of the cell can often be seen. They are much more nearly 
spherical and less irregular than the amoeboid cells. 

The large amoeboid leucocytes are more or less granular, and 
in certain lights these granules look quite dark and are some- 
times mistaken for bits of malarial pigment. This is especially 
true of the coarse granular cells seen occasionally; staining 
shows these large granules much more distinctly ( = eosino- 
phile — see below, p. 51) ; cells of this type are the most actively 
amoeboid of all. 

Q)) The most important i:>oint in connection with the leu- 
cocytes is their ratio to the red cells. This is estimated. in 
fresh specimens not by any actual counting but by reference to 
a standard fixed in the mind by study of normal specimens, and 
any considerable increase of the white cells would be noticed at 
once. Naturally we must not judge from any one part of the 
slide, as the distribution of the leucocytes may be unequal in 
different parts of it. 



PHYSIOLOGY OF THE BLOOD. 



41 



III. Blood Plates. 

Unless tlie number of these elements is increased by some 
pathological influence, we seldom notice them at all in normal 
blood. This is because we do not work quickly enough in pre- 
paring our specimen. Hayem recommends that the cover glass 
be laid upon the slide before the puncture is made, and as soon 
as the drop emerges it is allowed to run in between slide and 
cover by capillary attraction, thus avoiding contact with the air. ' 
The blood plates are irregularly shaped, very cohesive elements, 
about one-half the diameter of a blood disc, usually seen cling- 
ing together in masses like zoogloea. They are colorless and 
not amoeboid and look like debris. 




Fig. 15.— Rouleau Formation and Fibrin Network of Normal Blood. 



IV. Fibrin Netivork. 

After a specimen of fresh blood has stood for some time ex- 
posed to as much air as can creep in between slide and cover- 
glass, we begin to notice a network of fine straight lines in the 
spaces between the corpuscles. Here and there these filaments 

' This is a very satisfactory way if we wish to see the corpuscles as 
fresh and unspoiled as we can. Put a cover-glass on a slide so that the edge 
of one is just over the edge of the other, and, holding them in this position 
with finger and thumb, put their superimposed edges into the side of the 
drop as it emerges. It will run in between them by capillary attraction. 



42 



CLINICAL BLOOD EXAMINATION. 



seem to radiate from a centre where irregular, colorless masses, 
apparently blood plates, are to be seen (Fig. 15). 

No stain is needed to demonstrate these fibrin threads, but. 
a small-aperture diaphragm and very little light makes them 
plainer. Their only importance is that under certain pathologi- 
cal conditions the fibrin network is very much increased and 
helps us in the diagnosis (Fig. 16) . Hence it is of importance 




Fig. 16.— Increased Thickness of Fibrin Network. 



to be familiar with the ordinary closeness of the network in nor^ 
mal blood as a standard of comparison. 

For an account of the conditions of its increase see Chapter 
IX., page 107. 

Average Diameter of Red Cells. 

The blood under normal conditions shows considerable varia- 
tions in the size of its corpuscles in the fresh state as well as in 
stained specimens.' 

* A method of measuring, approximately accurate, and easily appli- 
cable in clinical work is the following : 

Using a camera lucida, trace on paper the divisions of a fine stage mi- 
crometer as seen under a one-twelfth oil immersion lens ; such micrometres 
are usually ruled to one-one-hundreth of a millimetre. Approximate ac- 
curacy in our tracing can be obtained if the process is repeated till the 
divisions marked in successive drawings correspond accurately one with 
another. Care must be taken that the paper is flat upon the table beside 



PHYSIOLOGY OF THE BLOOD. 



43 



The following table (v. Limbeck) shows the results of various 
observers. 



Normal Limits. Average Diameter. 

Welcker .diameter = 4. 5-9. 5 ju. '7 u 

Valentin 7 // 

Malinin 7.7ytt 

Hayem diameter = 6-8. Sfj-.. 7.5^ 

Mallassez 1.6 u- 

Laache diameter = 6-9 //.... S.5 /i 

Bizzozero 7. 075 fi 

Gram diameter = 6. 7-9. 3 /x 7.850 u 



Average = 7.5 lu 

These differences depend partly on differences in the method 
of measuring (wet or dry), and partly on the fact that the age 
and conditions of nutrition in the persons selected make a • 
difference. In the new-born, and to some extent throughout 
childhood, the normal limits of variation are wider than in adults 
(3.3-10.5 /J-, Hayem) . Sex appears to have no constant influence. 

Gram ^ noted that the measurements published by observers 
living in southern Europe are smaller than those of northern 
Europe (Italians 7-7.5, Germans 7.8, Norwegians 8.5). 

The majority of any individual's red cells are certainly about 
7.5 /J- in diameter, and this may accordingly be talten as our stand- 
ard (Hayem counts twelve per cent under 6.6 //-, twelve per cent 
over 8 p., the rest 7.5 p-). 

the microscope, and not raised on a block or otherwise ; also that the part of 
the paper on which we draw should be perpendicularly under the mirror and 
not off to one side. When a drawing has been made with these precautions, 
we have only to divide the space between each of the lines in our drawing 
into ten equal parts, and we have a ruler, each division of which repre- 
sents 1 /W as seen under a one-twelfth oil immersion lens, with the length of 
tube of the particular microscope used. To use our ^-ruler we have only to 
draw with the camera lucida any cell whose size we want to know, using 
always the same microscope, the same length of tube, and the same lenses, 
and having the drawing paper (as before) flat on the table and perpendic- 
ularly under the mirror. The drawing thus made is measured witli the 
i«-ruler like any other object. 

With this method a cell can be measured in a few seconds and with 
sufficient accurac}^ {i.e., within 0. 5 //). 

» Fortschritte der Medicin, 1884. 



44 



CLINICAL BLOOD EXAMINATION. 



Normal Number of the Eed Cells. 

1. At the level of the sea and in adult life the normal number 
of red cells per cubic millimetre is about 5,000,000 for men and 
4,500,000 for women. This is not infrequently increased in very 
vigorous, healthy persons; 6,000,000 is by no means rare among 
healthy young men, and higher figures are seen occasionally. 
Altitude above the sea level raises the count invariably (see below, 
page 65). 

2. The influence of menstruation, childbirth, and lactation is to 
diminish the red cells temporarily, the amount of the diminution 
depending not only on the amount of blood lost but on the 
capacity of the individual organism for blood regeneration. 
At puberty, when sexual functions are being established, we 
expect lower counts than after the establishment of the 
function. Normal pregnancy does not affect the count of red 
cells. 

3. The count of red cells per cubic millimetre is raised by 
any cause inducing concentration of the blood, such as profuse 
sweating, and is lowered by the temporary dilution of the blood 
after large draughts of liquid. In these changes, which are al- 
ways very transient, the haemoglobin and specific gravity in 
a given drop are of course increased with the corpuscles. 

Vasomotor influences affecting the calibre of the peripheral 
vessels (hot or cold baths, exercise, etc.) may temporarily con- 
centrate or dilute the blood by affecting the interchange of fluid 
between the vessels and the surrounding lymph spaces. By 
these processes the blood in the peripheral vessels may show an 
increase or diminution in the cellular elements, the haemoglobin 
and specific gravity corresponding to the greater or less concen- 
tration of the blood at that point (on these points see below 
page 63). 

Hayem noted that in young people especially the number of 
red cells varied considerably without any notable change in con- 
ditions. In adults the oscillations were much smaller. 

4. Influence of Nutrition on the Number of Bed Cells. 

A. After a meal, especially when considerable liquid is taken, 
the blood is temporarily diluted and hence the count of red cells 



PHYSIOLOGY OF THE BLOOD. 



45 



per cubic niillinietre is diminished (v. Limbeck; Reinert). 
This is illustrated by the following case from v. Limbeck. 

Adult, Male, Healthy. 



Red Cells. White Cells. Hb 

11 :15 A. M. 5, 580, 000 7, 660 98 per cent. 

12 M. dinner. 

12:15 P. M 5,320,000 6,166 

1:15 " 5,480,000 8,500 

2:15 " 4,733,000 12,000 

3:15 " 4,872,000 14,000 89 per cent. 

4;15 " 4,720,000 10,830 89 



As the white cells rise (digestive leucocytosis, see below, page 
83) the red fall. 

Fasting, by concentrating of the blood, temporarily increases 
the number of red cells (400,000-500,000 increase after twenty- 
four hours ' fast) . 

B. General Nutrition. — Lean, muscular people have on the 
average more red cells per cubic millimetre than fat peojjle 
(Leichtenstern, quoted by v. Limbeck), other things being 
equal. ' 

As above said, fasting (by concentrating the blood) raises the 
number of red blood cells, so that it is not simply hunger that 
gives us the diminution in red cells commonly found in poorly 
"nourished people, but rather the influence of bad hygiene in the 
slums, etc. 

5. Seasons and the time of day ^Q^m to have no influence in 
themselves. The same is true of race and climate. The only 
exception to this is reported in the work of E. Below, who 
found in yellow fever districts an average count of only 4,700,000 
red cells per cubic millimetre and the diameter of the individual 
cell reduced to 5.9 !j- on the average (7.5 p- = normal). 

6. Fatigue. — Hayem noted a loss of from 500,000 to 1,000,- 
000 red cells per cubic millimetre in the blood of a number 
of farmers after a hard summer's work, the counts made in 
September having been compared with those of April and al- 
ways found to be lower. Whether fatigue is the only cause of 
this diminution may be doubted. 

1 The influence of stasis in the obese, whose fat loads the surface of the 
heart, is to cause an apparent increase of red cells (see below, p. 60). 

2 "Deut. Tropenhygiene, " Berlin, 1895. O. Coblanz. 



46 



CLINICAL BLOOD EXAMINATION. 



7. Age. — In the new-born the number of red cells is very 
high for a few days (7,000,000 to 8,800,000), but falls at the 
end of seven to ten days (see below, page 86). 

In the very old a certain degree of anaemia is, so to speak, 
physiological ; but this, which like the plethora of the new-born 
is to be referred vot to the fact of age, but to concomitant influ- 
ences, is by no means invariable. Schmaltz reports 6,766,000 
red cells in a man and of eighty-one and 4,816,000 in a woman 
of seventy-four. 

Normal Number of White Cells. 

The figure usually given for adults is 7.500 per cubic milli- 
metre. This varies a good deal, according to the nutrition of 
the individual (see below, page 81) and also at different times 
of the day, owing to influences not explained. The influence of 
digestion will be mentioned later. In animals a slight shock ^ is 
sufiicient materially to affect the count of leucocytes; 5,000 to 
10,000 may be called the normal limits. There is, I believe, no 
evidence to show whether or not mental disturbances (fear, rage, 
emotion of various kinds) affect their number. Other causes of 
variation will be discussed under Leucocytosis. 

Blood Plates. 

The number of blood plates is from 200,000 to 300,000 under 
normal conditions. They are the chief constituents of white 
thrombi, and wherever they are diminished (e.g., in haemophilia, 
purpura) clotting is apt to be slow. They are increased in 
leukaemia and in many cases of grave anaemia. In the severer 
types of many infectious diseases (typhus, erysipelas, malaria) 
they are diminished, and in malaria they are sometimes wholly 
absent during the fever. In j^neumonia and tuberculosis they 
are normal or increased. In purpura and haemophilia they are 
sometimes much diminished or absent. 

The physiological limits of the amount of haemoglobin and 
of the specific gravity have already been mentioned. Under 
physiological conditions their variations follow those of the 
count of red cells. 

» Lowitt: "Studien z. Physiol, und Pathol, d. Blutes," etc., Jena, 1892. 
Fischer. 



CHAPTER V. 



FINER STRUCTURE OF THE BLOOD. 

I. Appearances of Dried and Stained Specimens. 

Cover-glass specimens prepared and stained as above di- 
rected give us more information of interest and importance than 
can be obtained from any other one method of blood examination. 
Approximate ideas of the quantity of red cells, of white cells, 
and of haemoglobin can be formed, parasites and bacteria can be 
seen, and the whole mass of evidence based on the finer structure 
of the leucocytes can only be obtained in this way. The ap- 
pearances of a specimen of normal blood prepared in this way 
are as follows : 

Red Cells. 

1. The hsemoglobin stains with the orange G of the tricolor 
mixture, and in a properly heated specimen the red cells are of a 
brilliant yellow or pale orange tint. If overheated they have a 
feebly stained, washed-out look, while if underheated they are 
more or less brown or gray. 

The degree of pallor of the centres corresponding to the 
amount of haemoglobin in the corpuscle can be gauged much 
more accurately with this stain than in the fresh preparations. 
The color of the edges is not much affected by pathological 
changes, the centres being the test. But in cases with extreme 
poverty of haemoglobin the colored rim may be reduced to a 
mere shell and the rest may be almost completely colorless. 
The power to estimate the amount of anaemia in this way can 
be easily acquired. 

An approximate idea of the number of red cells may be 
formed by any observer who has learned to use a uniform 
technique in each case and to spread the blood of a standard 
thickness. 

2. Nothing is seen of the fibrin or blood plates, as a rule. 
In normal cases the i)lasma does not stain at all. 



48 



CLINICAL BLOOD EXAMINATION. 



White Corpuscles. 

3. The chief purpose and use of the " triple stain" is for dis- 
tinguishing the varieties of white corpuscles, and the pathologi- 
cal states of the red. About the normal red cells it gives us no 
information that cannot be obtained as well by various other 
stains, but our knowledge of normal leucocytes has been im- 
mensely enlarged by its use. 

In normal blood stained as above directed, we recognize the 
following varieties of white cells : 

(1) Small lymphoctyes (see Plate I.). These consist mostly 
of a round blue nucleus about the size of a red cell, and sur- 
rounded by a thin coating of protoplasm, faintly stained or in- 
visible. 

The nucleus may be considerably smaller than a red cell, in 
which case it is almost certain to stain deeply, nearly black. 
The larger it is the more apt it is to be pale, as if there were a 
fixed amount of colorable matter which got spread out thin when 
the nucleus grew larger (see Plate I.). 

There is no line to be drawn between this form and that next 
to be described, namely, the "large lymphocyte" or "large 
mononuclear cells," which is simply larger and paler. 

The small lymphocyte is without much doubt the j^oungest 
form of leucocytes seen in the blood — that is, it is the white cor- 
puscle just after it has graduated from the adenoid organs where 
it is formed. It grows both by increasing its protoplasm and by 
increasing the size of its nucleus ; but the former grows faster 
than the latter, so that in the so-called "large lymphocyte" the 
nucleus occupies relatively less of the cell than when it was 
younger. 

In many cases we do not see in the blood all the stages of 
this growth. Lymphocytes are either "small" (5-10 /->■ in 
diameter) or "large" (13-15 p- in diameter) (see Plate I.). 

In other cases we find every intermediate size, both of nucleus 
and of the cells as a whole, and in such cases it is absurd to 
attempt a division into "large" or "small," though we may be 
able to say in a general way which size predominates. 

(2) The theory that the " large'' mononuclear cells come from 
the spleen and the small mononuclear from the lymph glands 



4 



PLATE I. 



Fig. 1. — (a) Polymorphonuclear NeutropMles. Note the varieties in 
size and shape of granules, the irregular staining of the nuclei, the light 
space around them, their relatively central position in the cell, 

(6) Myelocytes. Note identity of granules with those just described ; 
the even, pale stain of nuclei ; their position near the surface (edge) of the 
cell. The two cells figured indicate the usual variations in the size of the 
whole cell. 

(c) Small Lymphocytes. In the cell at the left note transparent proto- 
plasm ; in the cell next to it note vei^y pale pink ring of protoplasm around 
nucleus which is deeply stained, especially at the periphery. The next 
cell lias an indented nucleus ; its protoplasm relatively distinct. The cell 
on the extreme right shows no protoplasm and is probably necrotic. In all 
note absence of granules. 

(d) Large Lymphocytes. Note pale-stained nuclei and protoplasm, ir- 
regularity of outline ; indented nucleus in one. Every intermediate stage 
between these and the "smalV^ lymphocytes occurs, and the distinction 
between them is arbitrary. 

(e) Eosinophile. Note irregular shape, loose connection of granules, 
their copper color, their uniform and relatively large size, and spherical 
jshape. 

(/) Eosinophilic Myelocyte. Note similarity to (b) ordinary myelocytes 
except as regards granules. Color of granules may be as in (e) ordinary 
eosinophile. 

All the above were stained with the Ehrlich-Biondi mixture, and drawn 
with camera lucida. Oil-immersion objective one-twelfth and ocular No. 
iii. (Leitz). 

Fig. 2. — Malarial Parasites in Fresh (Unstained) Blood (Tertian 
Forms) . N, N, normal red corpuscles ; 1, red cell containing hyaline body ; 
2, 3, 4, 5, successive stages in the development of the parasite, showing 
acquisition of pigment ; 6, 7, full-grown parasites, the corpuscle no 
longer visible ; 8, beginning of segmentation ; 9, segmentation. In 6 and 
7 note brownish blur behind the pigment dots. Drawn as in Fig. 1. 

Fig. 3. — Tertian Parasite Stained ivith Eosin and Methyl Blue. The 
remains of the corpuscle containing the parasite stain pink, the parasite 
blue, and its pigment black. The stages of growth correspond with the 
numbers attached. Note in Figs. 1, 2, 3, and 4 the shape of the parasite, 
shown better than in fresh specimen. 

[Owing to a mistake the cells in Fig. 3 are not drawn according to a 
single scale and their relative sizes must be disregarded.] 



Examination of the Blood. 

PLATE I. 



Fig. 1. Varieties of Leucocytes. 



Polymorphonuclear 
neutrophiles — 




>.'- •; i;*"^*^— Myelocytes 



Small Lymphocytes 




.Large Lymphocytes 



Eosinophile 



f ... 





• Eosinophilic 
Myelocyte 



The Malarial Organism. 



It 



8 
.••"tV.'f 

%4 



7 



Fig. 2. 



Fig. 3. 



R. C. Cabot fee. 



Lith. Anst. v. E. A. Fnnkfl, Leipzig;. 



FINER STRUCTURE OF THE BLOOD. 



49 



has been abandoned by most writers of late years, and it is now 
generally supposed that all the leucocytes enter the blood (under 
normal conditions) as small lymphocytes and then grow up, the 
different forms seen in the circulating blood representing differ- 
ent stages of growth. 

The protoplasm of the lymphocytes, as has been said, is 
always hard to stain. Sometimes it has a faint pinkish tinge, 
more frequently it is grayish or very light blue, and in some 
cases it stands out brilliantly transparent and colorless against 
the faint purplish tinge of the surrounding plasma (see Plate I.). 

I have described the lymphocytes so far as "mononuclear," 
but it is not rare to find even very small ones (6 ij- in diameter) 
whose nucleus has a deep cut in one side or has divided into 
two parts. I believe it is commoner to find a nucleus in the 
small forms than in the "large lymphocytes." The inapplica- 
bility of the term "small mononuclear cells" or "large mono- 
nuclear cells " to this variety of corpuscle is evident. The dis- 
tinguishing mark is not the single nucleus but the absence of 
granules. 

In the younger and smaller forms of lymphocytes the 
nucleus, even when dividing, is compact and fills most of the 
cell. But as it grows older, instead of simply getting larger 
and paler, the nucleus may begin to bend and branch in the cell 
and then we get the so-called 

(3) " Transitional forms,'' which are no larger than the larger 
>size of lymphocytes, from which they differ only in that they 
have an indentation in their nucleus — either a narrow cut or a 
bay so wide that a "horseshoe" nucleus results. This is the 
transitional form according to this nomenclature. There is no 
reason for calling it so, as all the forms of leucocytes are transi- 
tional, but there is some convenience in the name. Like most 
large lymphocytes it is pale all through — pale in both nucleus 
and protoplasm — and often escapes notice in hasty examina- 
tions. Sometimes its protoplasm is sparsely covered with faint 
granules. 

(4) Next in age come the cells usually known as "polynu- 
clear" but more properly called polymorplionudear neutrophiles. 
These cells constitute the vast majority of those found in ordi- 
nary pus. The main difference between them and those last 
described is in the possession of granules, when stained by Ehr- 



50 



CLINICAL BLOOD EXAMINATION. 



lich's methods. The nucleus stains usually quite deep blue or 
greenish-blue, and irregularly, i.e., more intensely in some 
parts than in others. It is very irregular in shape, being 
twisted about in the body of the cell, possibly in consequence 
of its amoeboid movements. Here and there it may dive down 
so deeply beneath the surface of the cell that it is hidden 
under a thick layer of granules, reappearing in another i)art of 
the cell so that it seems to be broken in two. Occasionally, no 
doubt, this is actually the case, but generally there are " under- 
ground connections" between the apparently separate pieces of 
nucleus. Now and then we see a cell (degenerating) where the 
granules have fallen away, leaving the nucleus like a short, thick 
snake, very rarely two. 

One never sees any two of these cells whose nuclei are of the 
same shape. Hence the term "polymorphonuclear." The 
windings and twistings of the nucleus have suggested compari- 
sons to the letters Z, S, E, etc. 

The granules which fill the body of the cell and in which the 
nucleus is embedded stain well only with triple stains like 
Ehrlich's. Acid stains like eosin, and basic stains like meth- 
ylene blue, do not bring them out clearly. Hence the term 
"neutrophilic," which is not strictly accurate; more properly 
they are oxyphilic' With the Ehrlich-Biondi mixture they 
stain violet or purple, sometimes pink. They are very small 
and irregular in shape and size, contrasting with the large, 

round, " eosinophile" granules (see be- 
' - low). The cells being spherical the 

'""----.i^^^P.'i;, granules lie over and around the nu- 
'^jS^'^^' cleus, not simply at the side of it. In 
their interstices we seem to see a pinkish 
background of cell substance. These 
"neutrophilic" granules, which are so 
small that except with very high powers 
they look like a diifuse stain, are gener- 
ally developed only in the adult life of 
Fig. 17. the Cell. In normal blood we rarely if 

ever find them except in cells whose nu- 
cleus has reached the polymorphous stage. Occasionally we 
seem to see mononuclear neutrophiles, having a round nucleus 
' Ehrlich's stain is really a differential acid stain and not neutral. 




FINEK STRUCTURE OF THE BLOOD. 



51 



with neutropiiilic granules, but careful focussing usually shows 
that the appearance of a round or rod-shaped nucleus is given 
by the tight coiling of the ribbon-like nucleus round one of its 
ends, or else that a horseshoe nucleus is seen from the point of 
view indicated in Fig. 17. Thus if the eye be at the point A the 
nucleus will appear of the shape indicated in B. 

(5) If the variety of leucocyte last described is to be con- 
sidered as "adult" or "ripe," the eosinopMles will correspond to 
the old or overripe cell. There are some difficulties in the way of 
this hypothesis, but it is convenient to adopt it for the present. 

The " over-ripe" cell has, like its predecessor, a polymorphous 
nucleus and granules ; but the nucleus is paler and more loosely 
connected to the granules, and the latter are accurately spherical, 
of uniform size, and much larger than any seen in the neutro- 
philic cell. They have strong affinity for acid coloring matters 
(eosin, acid-fuchsin, etc.), hence their name. In specimens 
stained with simply eosin or eosin and methyl blue they are 
very brightly colored pink. With the Ehrlicli-Biondi mixture 
they are more of a copper or burnt-sienna color. Someind ivid- 
ual granules stain much darker than others in the same cell. 

The eosinophiles are the most activelj^ amoeboid of all the 
corpuscles, and it may be for this reason that the different parts 
of the cell seem so loosely strung together. The granules may 
be all at one side of the cell and the nucleus on the other, and 
in cover-glass specimens we very frequently find actual separa- 
tion of the two, whether or not by the technique of spreading 
the blood is unimportant, as we find such broken cells much 
more often among the eosinophiles than among any other 
variety — which argues a weaker structure. 

Sometimes there seem to be two or more distinct and separate 
nuclei in the cell, no " underground connection" being traceable. 
The granules are seldom over the nucleus as we see it in cover- 
glass preparations, but cluster round it loosely. 

The cell as a whole is usually a little smaller than the " neu- 
trophil" and more irregular in shape. In stained specimens 
the neutrophile is seldom seen with a pseudopod extended, 
whereas the eosinophile often shows it. 

The staining of the nucleus is more even as well as paler 
than that of the neutrophile, and with the Ehrlich-Biondi stain 
often has a robin 's-egg tint. 



52 



CLINICAL BLOOD EXAMINATION. 



The four stages of growth in which we usually find leucocytes 
in the blood are these : 

1. Small lymphocytes, 

2. Large lymphocytes and transitional forms, 

3. Polymorphonuclear neutrophiles — adult cells. 

4. Eosinophiles — old cells. 

5. A fifth variety of leucocyte— the basophilic "mast cell" — has lately 
been described as a constituent of normal blood, though in very small 
numbers. In leuksBraia it i-s not very uncommon, but no special signifi- 
cance is attached to it. 

With Ehrlich's stain the basophilic granules of this cell are not seen or 
appear only as clear white spots. Stained with the following solution 
they are easily seen : 

Dahlia (saturated alcoholic solution filtered) , ... 50 

Glacial acetic acid, 10-15 

Distilled water, 100 

Covers should be left twenty-four hours in this mixture, then washed 
and mounted in the ordinary way. The nucleus is usually polymorphous. 
Where these basophilic cells belong in the life history of the leucocyte is 
uncertain, and they have as yet no known clinical significance. 



young cells. 



Terms. 

No one can feel more unsatisfied with this terminology than 
the writer. It rests partly on a theory of the origin of the cells 
("lymphocytes"), partly on the properties of the nucleus ("poly- 
morphonuclear"), and partly on afiinities for aniline dyes ("neu- 
trophile" — " eosinophile"). 

All that can be said for it is that it discards certain very mis- 
leading names like " splenocyte" (a term applied by some to the 
large lymphocytes according to the now exploded theory that 
they came from the spleen), or like "small mononuclear" to 
designate cells not rarely polynuclear. 

The cumbrous word " polymorphonuclear" is a shade better 
than "polynuclear," and that is all to be said in its favor. 

It is greatly to be hoped that we may ere long have a new 
and improved terminology by some competent student. While 
waiting for this the writer has thought it best to save time and 
space by speaking of them often as "young," "adult," and 
"old," with the meaning indicated above. 

For some unknown reason we do usually find the leucocytes 



FINER STRUCTURE OF THE BLOOD. 



53 



only at these four isolated stages of growth (the frequent 
presence of transitional stages between "small" and "large" 
lynaphocy tes has been mentioned as an exception) . Apparently 
they must pass comparatively rapidly through certain stages 
and remain longer in others, or it may be that they retire out of 
the peripheral blood at certain periods of the growth. 

It is certainly curious how rarely we find a lymphocyte just 
beginning to accumulate neutrophilic granules. They seem to 
jump from non-granular to profusely granular, and we rarely see 
any of the intermediate stages. 

Still rarer is it to find any link between neutrophilic and 
eosinophilic cells. A few instances have been reported (in 
pathological blood) where both kinds of granules were present 
in a cell, or granules of an intermediate description. But this 
has been denied by excellent observers and must certainly be 
very rare. 

Normal Percentage of Each Variety. 

In the blood of healthy adults the proportions of the different 
varieties above described are the following : 

^ j small lymphocytes, .... 20-30 per cent. 

^^"""^ ( large " * .... 4- 8 " 

Adult (polymorphonuclear neutrophiles), . 62-70 " 
Old (eosinophiles), ...... i- 4 " 

"Mast cells," To i " 

In infancy the percentage of young cells is much larger (forty 
to sixty per cent) and the adult cells (polymorphonuclear) are 
only eighteen to forty per cent. 

In a variety of debilitated conditions not usually thought of 
as definite diseases, the number of young cells is comparatively 
large and that of the adult cells small. The general vigor and 
health of the individual can sometimes be estimated simply from 
the forwardness or backwardness of their blood development 
as mirrored in the leucocytes. Persons calling themselves well, 
but never vigorous or active, may show no more than fifty per 
cent of adult cells, the young cells running up to forty or even 
fifty per cent. 

Not all cases of debility show this change, and we are not 
yet in a position to say under just what conditions it occurs. 



54 



CLINICAL BLOOD EXAMINATION. 



Presumably the conditions are such as decrease the nutritive 
value of the plasma. 

The same change in frankly pathological conditions will be 
discussed later (page 98) . 

So far I have spoken only of those changes in the percen- 
tages of different leucocytes which are to be explained by a 
more or less rapid metabolism of the cells themselves in the 
blood, as if they were always sent into the blood as young lym- 
phocytes and lived and died there. 

But the eosinophils often change their number in a way 
hard to explain on this hypothesis. We know that eosino- 
philes are present in large numbers in various parts of 
the body outside the blood-vessels (bone marrow, thymus 
gland), and in many ways they seem to live their life in 
comparative independence of the other members of the leu- 
cocyte group. 

In the free interchange of fluid and cells that is constantly 
going on between blood-vessels and lymphatic tissues and spaces, 
it is e^ddent that a part of the life history of the leucocytes goes 
on outside the vessels, and there is reason to suppose that it is 
largely or partly outside the vessels that cells of a given age 
divide and produce others like themselves, while in the blood- 
vessels they simply grow up without such division. At any 
rate, we rarely find evidence of mitosis or amitosis in the circu- 
lating leucocytes, while in the lymph glands and the marrow, and 
sometimes elsewhere, such dividing forms are more common. 

The bone marrow seems to be ^uch a dividing-place for 
eosinophils. They are always numerous there and mitoses are 
often seen in them. Indeed their number is so small in normal 
circulating blood that they might almost be said to be there " by 
mistake," belonging normally elsewhere. Whether or not this 
has any connection with their very active amoeboid properties, 
I do not know. The " mast cells" are even more " an accident" 
in the blood, and Ehrlich denies that they are a constituent of 
normal blood. 

An increase of eosinophilic cells in the peripheral blood 
does not seem to mean simply a change in the rapidity of meta- 
bolism, but to point sometimes to a disturbance having relation 
to the places or functions which produce them. The eosino- 
phile, therefore, more than any other cell normally present in 



FINER STRUCTURE OF THE BLOOD. 



55 



blood, has value in diaguosis by pointiDg to the location of a 
disease (see below, page 100) . 

Their increase and decrease in the circulating blood does not 
follow that of the other ripe cells (neutrophiles), in fact is often 
inversely proportional to it, and they are often markedly in- 
creased in a blood otherwise normal, sometimes for reasons 
wholly unknown to us. 

An increase in the lymphocytes or neutrophiles does not 
occur without other blood changes, and points, not to disease of 
one place or function, but to general conditions like inflamma- 
tion or malnutrition. 

I have spoken of the eosinophiles and " mast cells" as com- 
parative strangers, though not intruders in the circulating blood. 
They are thus intermediate between the regular inhabitants 
(lymphocytes and neutrophiles) and the variety next to be men- 
tioned, which are real intruders — i.e., never found in normal 
blood. These are the 

Myelocytes (Ehrlich). 

The normal abiding-place of these cells appears to be the 
bone marrow, hence their name of myelocytes or marrow cells. 
They are perhaps the most numerous leucocyte to be found in 
the marrow, although lymphocytes and polymorphonuclear cells 
are also to be found there, and eosinophiles are numerous. 

I describe them here because they are peculiar to no one 
disease and are occasional visitors of the blood in conditions on 
the borderland between the pathological and the physiological 
(starvation — various intoxications) . 

The myelocyte (see Plate I.), like the polymorphonuclear 
neutrophile, is recognizable only by Ehrlich's staining methods. 
With the Ehrlich-Biondi stain it appears as a spherical cell 
nearly filled b}^ a large, pale-stained nucleus immersed in neutro- 
philic granules. You see at once how little it differs from the 
large lymphocytes (simply in having granules) and from the 
polymorphonuclear neutrophile (only in the shape of its nucleus). 
Were it present in normal blood we should imdoubtedly consider 
it an intermediate stage between the large lymphocyte and the 
polymorphonuclear neutrophile. I see no sufficient reason for 
thinking otherwise merely because it does not appear in normal 



56 



CLINICAL BLOOD EXAMINATION. 



blood. The leucocytes are so cosmopolitan in their habits that 
we can hardly call them blood cells at all. It is better to think 
of "blood leucocytes," "gland leucocytes," and "marrow leu- 
cocytes" (perhaps "skin and mucous membrane leucocytes" too, 
see below, page 101) and to consider that "missing links" among 
blood leucoc\^tes are to be looked for among those that live and 
grow up elsewhere. Presumably the conditions in the marrow 
(nutrition?) are such as bring out sides of the leucocyte nature 
suppressed in the blood. 

The granules of the myelocyte are precisely those of the 
adult blood leucocyte and need no second description (see 
Plate I. ) . The nucleus, by which alone we distinguish it from 
the adult blood leucocyte, shows none of the twists and turns 
characteristic of the latter. Presumably this is due to the fact 
that the myelocyte is not amoeboid and so does not mutilate its 
nucleus in the trying process of crawling through tissues and 
vessel walls. 

1. The myelocyte nucleus, then, is usualh^ spherical or egg- 
shaped, and is in close contact with the cell wall for a compara- 
tively large portion of its extent — i.e., if egg-shaped it is placed 
eccentrically. 

2. The absence of amoeboid motion and of journeys through 
tissues leaves the nucleus evenly and moderately stainable 
throughout, while the amoeboid blood leucocyte, through the 
wear and tear of its migrations, gets its chromatin irregularly 
distributed, condensed here, pulled out thin there, and hence 
stains unevenly or is mottled. 

Not infrequently the nucleus shows signs of old age 
(vacuoles) or of mitosis, and occasionally we find two nuclei at 
the poles of the cell. It is then to be distinguished from the 
adult blood leucocyte (polymorphonuclear neutrophile) by the 
fact of its having the nucleus in close contact with the surface of 
the whole cell for a comparatively large portion of its extent, 
while in the adult blood leucocyte the nucleus abruptly leaves 
the surfaces again if it chances to approach it. The poly- 
nuclear myelocyte is also to be distinguished from the poly- 
morphonuclear neutrophile by the even staining of the nucleus 
in the former. 



FINER STRUCTURE OF THE BLOOD. 



57 



She of Myelocytes. 

Every account of the myelocyte which has come to my notice 
speaks of them as very large cells, the largest variety of leu- 
cocytes ever seen in the blood. 

Ihis is true of many of them ; diameters of 18-21 m are not 
uncommon, but we also find them of every other size down to 
10-11 /J. diameter, that is, down to the size of a lymphocyte. 
This is true both of the myelocytes in the circulating (leukgemic) 
blood and of those in the marrow. No distinction from other 
varieties of leucocyte can be based on size alone, unless we say 
their average size is greater than the average size of the leu- 
cocyte. Perhaps the following table may be of interest : 

Average diameter of 100 myelocytes = 15, 75 lu. 

" " " 100 polymorphonuclear neutrophiles = 13. 50^. 

" " " 100 "large" lymphocytes = 13 itf. 

." " " 100 eosinophiles = 12 n. 

" " " 100 "small" lymphocytes = 10//, 

" " " 100 red corpuscles (normal) =7.5 ju. 

Eosinophilic Myelocytes. 

Under the same conditions where we expect to find the or- 
dinary (neutrophilic) myelocyte, we often find a small number 
of cells identical with them in all respects, except in possessing 
eosinophilic in place of neutrophilic granules. Such cells are 
found in abundance in the marrow, and this fact together with 
the resemblance to the ordinary myelocyte both in morphology 
and in the conditions of their occurrence, seems to me to justify 
the term eosinopliilic myelocyte. 

Coenil's "Mark Cells." 

By most observers these are supposed to be the same as 
Ehrlich's "mark cells" or myelocytes. Cornil worked before 
the days of Ehrlich's staining methods and therefore before the 
presence of neutrophilic granules could be used to distinguish a 
myelocyte from a large lymphocyte. Cornil' s description of 
them would answer for either. Schreiber considers Cornil to 
have discovered a different variety of non-granular cell, but the 



58 



CLINICAL BLOOD EXAMINATION. 



description of it given by Sclireiber seems to me to leave it in- 
distinguishable from a large lymphocyte. 

Mononuclear Neutrophiles. — Capps' observed in general paralysis of 
the insane a variety of leucocyte possessing a deep-staining centrally 
placed nucleus like that of a lymphocyte, but containing also neutrophilic 
granules. He considers it either a variation from the ordinary type of 
marrow-bred cell visiting the blood temporarily, or more likely an ordi- 
nary lymphocyte in which the granules have developed before the nucleus 
has become polymorphous. Thayer has observed similar cells, but has 
given no explanation of them. Klein ^ mentions them under the name 
above given and figures them in his plate, but does not comment on them. 

So far I have described the type cell of each variety. As we 
should expect, atypical forms are numerous. Some of the com- 
moner ones are as follows : 

1. Young cells whose ]iucleus is pale blue instead of dark 
blue. 

2. Cells more developed but sfcill non-granular, whose proto- 
plasm has evidently forsaken them. 

3. Cells on the borderland between the "marrow cell" and 
the "adult blood leucocyte," the nucleus having some of the 
characters of each variety. 

4. Cells the nature of whose granules we cannot settle (eosi- 
nophilic or neutrophilic). 

Other rare varieties will be mentioned under leukaemia. 

^ American Journal of Medical Sciences, June, 1896. 

2 Volkmann's Sammlung klin. Vortrage, December, 1893. 



PART III. 

GENERAL PATHOLOGY OF THE BLOOD. 



CHAPTER yi. 

UNEQUAL DISTRIBUTION OF BLOOD— PLETHORA— DILUTION 
AND CONCENTRATION OF THE BLOOD. 

I. Unequal Distribution. 

How far is the single drop used for blood examination typi- 
cal of the whole? 

It has been experimentallj^ proved that specimens of the 
blood of the smaller venous and arterial twigs do not differ 
from each other materially in corpuscular richness. Capillary 
blood is slightly richer in corpuscles than that either of veins 
or of arteries. But as capillary blood is everywhere of the 
same corpuscular richness, we may consider one capillary net- 
work or set of venules as typical as another, provided our tech- 
nique is good, that is, provided lymph is not squeezed into the 
drop by strong pressure. It is indifferent, therefore, so far as 
accuracy is concerned, whether the drop of blood be obtained 
from one or another part of the body. All standard estimates 
of the number of corpuscles per cubic millimetre of normal 
blood refer to capillary blood. 

2. Apparent Polymjtlia^mia. 

So far we are speaking of normal conditions. It is a famil- 
iar fact, however, that the vessels of a given part of the body 
can be overcrowded with blood, e.g., by the use of an Esmarch 
bandage. A drop taken from such a part would certainly not 
be typical. Now as the same effect can be produced by a 
variety of diseases, under these conditions we must modify 
considerably any inferences made from examination of a single 
drop. 



60 



CLINICAL BLOOD EXAMINATION. 



Such conditions, entailing a false polvcythsemia or apparent 
increase in the number of corpuscles are : 

I. Any disease inyolving either (a) general cyanosis or (b) 
cyanosis of the part from which the drop of blood is drawn. 

(a) General cyanosis results either from cardiac insufficiency 
(valvular or parietal disease of the heart itself, blocking of the 
lung circulation by em]physema or thrombosis), from insufficient 
aeration of the blood (pneumonia, congenital malformation of 
the heart), interference with the heart's action b}' pressure of 
tumors, effusions (pericardial, pleural, peritoneal), or enlarged 
organs (liver, spleen), or from vasomotor disturbances. It is 
evident that some of these conditions {e.g., congenital heart 
disease) may not involve any peripheral stasis at all, and in the 
absence of this it is not easy to account for the increased number 
of corpuscles in the droiD. Some observers have supposed that 
there is a real overproduction of blood cells under these condi- 
tions ; others suppose that the life of the individual corpuscle 
being lengthened, reproduction of cells at the normal rate soon 
leads to the "glut." There seems to be no reason to suppose 
that there is in these cases any unequal distribution of cells in 
favor of the periphery, such as is obviously the condition in 
ordinary cyanosis with stasis. Whatever the explanation may 
be, there is no doubt of the fact that general cyanosis from any 
cause whatever produces an increase of cells in a drop such as 
we usually examine. 

The cases of cyanosis which I have classed under " vaso- 
motor" (for want of a better explanation), cases in which, in the 
absence of disease in any organ, the skin and mucous mem- 
branes are persistently and markedly bluish, are not very 
uncommon. I have seen three such, all in stout, elderly 
women. In one the cells in a drop of blood from the ear, 
finger, or toe were more than dofihJe the normal number (see 
below, page 67) . 

(6) Local Cyanosis. — The pressure of a tumor, or any other 
hindrance to the circulation of any part, may give a similar in- 
crease in the number of corpuscles in a measured amount of 
blood from that part. Here again vasomotor conditions may 
cause cyanosis and apparent polycythsemia. 

In markedly cyanotic patients the count of red cells is notably 
above normal, we should naturally guess the reason, and make 



GENERAL PATHOLOGY OF THE BLOOD. 



61 



allowances. Error is more likely to arise where we have cyanosis 
in a person whose blood is poor in red corpuscles. The combi- 
nation of these two factors may give us a normal blood count and 
lead us to overlook the anaemia. Thus a person might have 
really a severe anaemia and yet the count of red cells be actually 
above the normal. This element of stasis should never be lost 
sight of. Many high counts reported in pneumonia or hysteria 
are to be explained by abnormalities not of i^'^oduction or destruc- 
tion but of distribution of the blood cells. 

II. Certain patients, whoso circulations are feeble without 
being feeble enough to produce actual cyanosis, first give us 
evidence of the fact by an increase in the count of blood corpus- 
cles in a given amount of peripheral blood. Following up the 
hint thus given, one md,j sometimes be brought to note and in- 
vestigate an element in the case which might otherwise have 
been lost sight of. 

With these exceptions the drop of blood taken at the periph- 
ery is typical. We have next to consider some general condi- 
tions under which a person's whole blood may be inferred to be 
abnormal from the findings in a drop taken from the periphery. 
Consideration of special diseases will follow later. 

Full-Bloodedness (Plethora) and its Opposite. 

There is no direct evidence for the existence of any long- 
standing over-filling or under-filling of the blood-vessels ; there 
is a good deal of experimental evidence to show that if by arti- 
ficial means we succeed in forcing into the vessels an abnormal 
amount of fluid (transfusion of blood or normal salt solution — 
large draughts of water), it does not stay there many hours, but 
comes out by the kidneys. 

The red-faced persons popularly known as "full-blooded" 
show no abnormalities in their blood discoverable by any means 
of investigation known to us. The condition is probably de- 
pendent on the presence of a rich capillary network near the 
surface of the skin, or a dilatation of individual venules and 
arterioles at the periphery. Such a person may be markedly 
anaemic without any considerable changes in the color of the 
face. The fact that people of such complexion often end their 
lives with a ruptured cerebral artery is due presumably to the 



62 



CLINICAL BLOOD EXAMINATION. 



circumstaDce that " high living" produces in the same individual 
dilated peripheral capillaries and weakened arterial walls. 

Temporary increase or diminution in the amount of fluid with- 
in the vessels can be brought about not only by a change in the 
mechanical conditions of pressure and osmosis, but by any influ- 
ence affecting the tone of the peripheral vessels. "We have then : 

(a) Temporary serous pletliora or dilution of the blood from 
transfusion of fluid in large amounts or its ingestion by mouth 
or rectum. 

(b) From decreased blood pressure, as in acute failures of 
compensation in cardiac disease. 

(c) From vasomotor dilatation. 

As an example of this last Grawitz reduced the specific grav- 
ity of the blood from 1041 to 1038.7 within eight minutes by 
the inhalation of nitrite of amyl. This decrease of specific grav- 
ity can only mean an increased amount of watery constituents in 
the blood, as there was no evidence of any destruction of the 
heavier elements of the blood, and orAj water (and chlorides) 
pass through the vessel walls easily. In the above case the 
specific gravity was again at 1041 within a few minutes. 

{d) In cases of severe anaemia which recover, the blood regen- 
eration may attain such vigor that the number of red cells shoots 
up above normal, even as high as 7,700,000. This is temporary 
cellular pletliora or polycythsemia. 

(e) The same condition can be temporarily produced by 
transfusion of actual blood from one individual to another. It 
lasts but a few days as a rule. 

The polycj^thgemia of the new-born will be discussed later. 

Concentration of the Blood. 

It is obvious that influences opposite to those producing 
temporary full-bloodedness will produce temporary lack of fluid 
within the vessels. So acute diarrhoea, purgation, deprivation 
of liquids (as in starvation), rapidly accumulated serous effu- 
sions, profuse vomiting or sweating (by skin and lungs) producp- 
a temporary concentration of the blood by draining out its diffus- 
ible elements (water chiefly) . All these influences are transitory. 
More permanent drains on the system, like chronic diarrhoea, 
diabetes insipidus or mellitus, or long-standing suppurations, 
tions of blood volume that we can measure the amount lost by 



GENERAL PATHOLOGY OF THE BLOOD. 6li 

show no evidence of lessening the volume of blood in the vessels. 
They drain albumin out of the serum and corpuscles and so 
decrease the weight of the blood (see below, page 71) , but the 
blood volume is not changed. Indeed, any influence has to work 
very quickly in order to concentrate the blood, for in an aston- 
ishingly short time the other tissues repay the vessels their loss 
of fluid and the normal blood volume is restored. 

The same temporary effects can be produced by influences con- 
stricting the vessels (cold, pain, suprarenal extract) , and a concen- 
tration of the blood results which lasts a few minutes or hours.' 

In all these interchanges of contents between the blood- 
vessels and the other tissues it is, as above said, the watery ele- 
ments chiefly that change. The red cells are not affected by the 
give-and-take of the vessels and tissues, and although cold pro- 
duces in the peripheral circulation an increase in the number of 
v/hite cells greater than can be accounted for by simple concen- 
tration, the weight of evidence seems to be against any new pro- 
duction of cells and in favor of a change only in distribution, 
the white cells accumulating at the periphery. 

Now as the number of cells is not affected by these tempo- 
rary variations in the volume of liquid within the vessels, it fol- 
lows that the number to be counted in a cubic millimetre, though 
typical of the whole blood at that time, is not to be reckoned from 
in the ordinary way. For example, after a severe diarrhoea or in 
phthisis after a night-sweat the blood may be temporarily so 
concentrated that Ave find 6,000,000 or more red corpuscles per 
cubic millimetre. Under normal conditions of the blood mass 
we should infer from such a count that the body contained one- 
sixth more red corpuscles than usual. Here obviously it only 
means (if anaemia is absent) that the blood mass is reduced by 
one-sixth by concentration. It is only in such sudden reduc- 

' Oliver has shown recently (Lancet, June 27th, 1896) that any influence 
causing rise of blooti pressure will slightly concentrate the blood. Thus 
raising the arm over the head and holding it there by muscular effort 
slightly concentrates the blood in that arm. Electrical stimulation or 
massage of the arm has the same effect. Loimrmg blood pressure, as 
when the arm is supported passively over the head, dilutes the blood. This 
confirms the results of Mitchell (Med. News. May, 1893) and of Cheron 
(Comptes Rend, de I'Acad. d. Sciences, 1896, No. vi.). Oliver uses a 
new method for estimating the number of red cells, the accuracy of which 
has not yet been tested by others. 
5 



64 



CLINICAL BLOOD EXAMINATION. 



this method. Loiig-stancling causes of drain on the plasma 
might at any time act as destroyers of red corpuscles as well, 
through the changes in the nutritive Huids in which they live. 

Fui'ther, it is only where we know the number of corpuscles 
just before the sudden drain on the x)lasma comes, that we can 
measure the amount of plasma lost by the amount of apparent 
increase in the red cells. Stasis and any other cause that heaps 
u\) corpuscles at the periphery must also be excluded before we 
can judge of the loss of plasma in this way. 

The conditions of an abnormal concentration of the blood are 
those already alluded to as temporarily sucking away its watery 
<?onstituents, namelj' : 

(a) Watery diarrhoea, especially in cholera and other acute 
diseases accompanied by diarrhoea ; 

{h) Large and rapidly accumulating serous effusions (slow 
accumulations would give time for the blood to take up water 
from the tissues and make up for its loss) ; 

(c) Profuse sweats ; 

{d) Persistent vomiting or starvation of liquids ; 

(e) Increased blood pressure (exercise, massage, electricity). 

Blood already lacking in red cells, if suddenl}^ concentrated 
by such a loss of fluid, might deceive us into supposing it 
normal, because the number of cells in a cubic millimetre might 
be normal. Li the presence, therefore, of an// such reason, for 
concentration of the blood, we should ahcaijs ntodifij our ordi- 
nary methods of inference from the Mood count. For example, 
T. Limbeck records a case of hepatic cirrhosis with ascites, 
where before tapping the ascites the count of red cells Avas 
3,280,000 per cubic millimetre. Within twenty -four hours after 
tapping there were 5,160,000 cells i)er cubic millimetre, the 
reaccumulation of the ascitic fluid going on so fast that the 
blood was unable to adjust itself and became overconcentrated. 
A careless observation might have inferred a great gain in the 
corpuscular richness of the whole blood, when in fact not a cor- 
puscle has been gained and those present have probably grown 
poorer in albumin. 

Dilution of the Blood. 

Causes of temx)orary dilution of the blood are less common 
than those of temporary concentration. 



GENERAL PATHOLOGY OF THE BLOOD. 



65 



Immediately after the inlialation of nitrite of amyl or the in- 
gestion of a large amount of fluid by mouth or rectum, the blood 
would be diluted so that a blood count would show a diminu- 
tion in the number of cells per cubic millimetre, which yet 
would be due to no changes in the number of red cells in the 
body, and might be wrongly taken for an ansemia. The dilu- 
tion in cases of heart disease will be discussed later (see p. 256). 
Any condition involving lowered blood pressure has the effect of 
diluting the blood by allowing the entrance of perivascular 
lymph. 

Summing up the discussion so far : There is no evidence for 
a chronic plethora nor for a chronic diminution in the volume of 
the blood. Where such takes place temporarily, it is by the ad- 
dition or subtraction of water and salts only, and not of the cor- 
puscles or organic materials, so that we must guard against false 
inferences from the resulting apparent increase or decrease of 
corpuscles per cubic millimetre. 

But although there is no positive evidence of a true increase 
in the whole amount of blood in the vessels (except temporarily) , 
there are some conditions which lead to an increased richness of 
the peripheral blood in red corpuscles even after excluding the 
influence of stasis or loss of fluid. Such a condition of what 
appears to he true polycythsemia is found: 

1. In persons living at high altitudes; 

2. In persons suffering from phosphorus or CO poisoning. 



1. The Blood in High Altitudes, 

The polycythsemia of those living at high altitudes increases 
the higher one goes. Koppe ' gives the following tables : 



Place. 


Height above 
sea level. 


Red cells. 


Author. 


Christiania 

Tubingen 

Zurich 

Auerbach 

Arosa 


O 

148 metres 
314 

414 " 

425 " 

700 " 
1,800 " 
4,392 " 


4. 974, 000 
5, 225, 000 
5,322,000 
5, 752, 000 
5,748,000 
5.900,000 
7,000,000 
8,000,000 


Laache. 
Schafer. 
Reinert. 
Stierlin. 
Koppe. 

Egger. 
Viault. 



^ Miinch. med. Woch., 1890, No. 41. 



66 



CLINICAL BLOOD EXAMINATION. 



This extraordinary change takes place within two weeks of 
the time of taking up residence in a high place, and independent 
of any change in diet or manner of living. The sick and the 
well are equally affected and animals show similar changes. 
The haemoglobin is also considerably increased, although it lags 
somewhat behind the corpuscles. 

Koppe states that the individual corpuscles under these con- 
ditions are so much smaller that their volume in a given 
amount of blood (as determined b}' the haematocrit) is not in- 
creased at all. 

On returning to low land, the blood returns within a short 
time to its normal condition. 

Many explanations have been offered for this interesting 
phenomenon. If it were a true new production of corpuscles we 
should expect some signs of blood destruction (icterus, hsemo- 
globinuria) on returning to the sea level. But there are no such 
signs. On the other hand, if the polycythsemia were a simple 
result of concentration due to the dryness of the high air, one 
would expect that the blood Avould quickly adapt itself, as in 
other (temporary) concentrations, by taking up water from the 
tissues. But in fact it does not do so. Possibly it may be ex- 
plained, as Pick suggests, by a lengthening of the life of individ- 
ual cells. 

2. Phosphorus . and CO Poisomng. 

The polycythsemia of acute phosphorus poisoning may 
reach as high as 8,650,000. This may be pai-tly explained by 
concentration due to the occurrence of vomiting, but in some 
cases the increase seems out of proportion to the amount of 
vomiting. 

With illuminating-gas poisoning there is usually no vomiting 
to speak of, and the cause of the marked increase in the red 
cells is unknown. Yon Limbeck in two cases showed respec- 
tively 6,630,000 and 5,700,000 red cells. Munzer and Palma ' 
record 5,700,000. The white cells are also increased (see below, 
page 94). 

Possibility of a true Plethora. 

Although there is no direct evidence that the whole blood 
mass in its relation to the weight of the body ever varies more 
iZeit. f. Heilk., vol. 15, p. 1. 



GENERAL PATHOLOGY OF THE BLOOD. 



67 



than temporarily from the traditional 1 to 13, one can hardly 
help getting the impression from certain patients that their 
blood mass is diminished, though we cannot prove it. Thus in 
certain cases of phthisis in which in spite of all the signs and 
symptoms of anaemia the blood count is normal, and simple con- 
centration of a really anaemic blood seems to be excluded by 
the absence of a cause for such concentration, we cannot help 
thinking that the whole amount of blood is too small. Again, 
it is possible that in individuals who eat and drink much and 
exercise little the blood-vessels may gradually accommodate 
themselves so as to hold a large bulk of liquid, and thus a true 
plethora or " full-blooded" condition might be brought about. 
Experiments show, however, that fat, "sedentary" animals 
(pigs) have less blood in proportion to their weight than lean, 
active animals (horses, dogs). Pigs' blood is only one twenty- 
second of their total weight, while horses' is one-tenth. 

Young, fast-growing animals have relatively more blood than 
adults, and males more than females. Our impression that old 
people are more or less " dried up" gets some support from the 
analogy of these animal experiments. 

Until some method is devised for estimating the total amount 
of blood during life, we shall never be sure upon this point. 



CHAPTEE YII. 



ANEMIA AND HYDR^xMIA. 

1. An^mla.. 

In the absence of an}' proof tliat tlie total volume of blood 
can be more than temporarily diminished, our definition of 
anaemia must be this: A deficiency in corpuscle substance, i.e., 
a deficiency in red corpuscles, in haemoglobin, or in both. 

It is important to bear in mind that the color of the skin is 
not a safe guide in judging whether a person is anaemic. Thus 
out of 100 cases shown to be anaemic by actual blood examina- 
tion, Townsend ' found a good color in the cheeks of 4 and a 
fair color in 7 others. Eighty-nine were pale. The color of 
the lips is but little better as a guide, as the following table 
from Townsend' s article shows : 



Table of Color in One Hundred Cases of Anaemia. 





Pale. 


Fair, 


Good. 


Nails 


95 


5 


0 




89 


7 


4 




84 


15 


1.3 




76 


21 


2.4 


Conjunctivae 


64 


25.5 


10.5 



My own impression would be that the lips and conjunctivae 
were better guides than they are shown to be in this table. 

In examining the color of the nails, the fingers should be 
flexed, as full extension may partlj^ cut off the circulation under 
the nails. 

A. K. Stone ' and his assistants estimated the haemoglobin 
of 189 female patients who looked anaemic, and found over 75 
per cent of haemoglobin in 89, or nearly one-half of them. For 

1 Townsend : Boston Medical and Surgical Journal, May 28th, 1896. 

2 Boston Medical and Surgical Journal, August 23d, 1894, 



ANEMIA AND HYDREMIA. 



69 



a woman a lisemogiobin percentage of 75 per cent or more 
means practically normal blood. ' 

The most striking example of the fallacj^ of judging of 
anaemia by the color of the skin and mucous membranes is in 
the so-called " tropical ancemia.'' Practically all persons belong- 
ing to white races who take up their residence in the tropics 
acquire after a time an extreme pallor of the skin and mucous 
membranes, and this appearance has usually received the title of 
"tropical anaemia." It turns out, however, from the careful 
studies of several different investigators, that the blood of such 
persons shows absolutely no anaemia or other variation from 
the normal. The api^earance of the skin is probably due to the 
action of the extreme climate on the peripheral nerves and 
vessels. Tropical anaemia is a condition not of the blood, but 
of the skin and subcutaneous tissues. 

Every one's experience includes a few persons who are per- 
fectly well despite an almost bloodless condition of the skin. 

On the other hand, anaemia may exist where there is a good 
color in the face (see above, page 63). 

We are to judge of anaemia, then, solely by the blood exam- 
ination, and this judgment can be accurately made on the basis 
of the small fraction of a drop used for examination, provided 
always that our technique is good, and provided we make allow- 
ances for a considerable error wherever there is reason to sup- 
pose that any venous and capillary stasis is present, or that the 
blood is temporarily concentrated or diluted (see above, page 
59). 

Distinction between Primary and Secondary Anwmia. 

In one sense all anaemia is secondary. It is due to some 
cause, a symptom in a chain of events. But in some cases we 
know the cause and in some we do not. 

(a) Primary anaemia is that in luhicli the causal factors are 
either entirely unknown or are insufficient to cause so severe a 
disease. This division, like most of our statements about the 
blood, is a rough-and-ready one, held to provisionally until a 
better classification is discovered. It has a certain utility if not 
used with any less simple meaning than that given above. 

' Where the lisemoglobin is high tlie number of corpuscles is never 
considerably diminished. 



70 



CLINICAL BLOOD EXAMINATION. 



In view of our ignorance of the blood-making functions, there 
is little difference between saying that a primary anaemia is a 
disease of the blood-making organs and saying that it is one 
whose cause is unknown, esi)ecially as the pathological appear- 
ances in the bone marrow recorded in cases of so-called primary 
anaemia do not differ from those which can be brought aloout 
exjDeri mentally by bleeding. There is no evidence that there 
are an}^ primary diseases of the blood-making functions. A 
case of secondary anaemia is one in which we have an ob^dous 
cause such as hemorrhage or malaria for the loss of corpuscle 
substance. Remove the cause and the anaemia ceases. Some- 
times, however, after removal of the cause, e.g., after cure of a 
case of syphilis, the anaemia set agoing by the syphilis i^ersists. 
Here we have to say that the anaemia has changed from " secon- 
dary" to "primary," x^ossibly through some alterations pro- 
duced in the blood-making functions which disable them from 
making up the lost blood, even though the drain ui)on it is no 
longer going on. On the other hand, there are few cases of 
" primary" anaemia who cannot recall some event in their past 
lives sufficient to account for a certain grade of ameraia {e.g., 8b 
nervous shock, a hemorrhage, an attack of tertian malaria). 
Tet if the anaemia that occurs after so slight a cause is of the 
pernicious or fatal type, we may fairly call it ''primary.'' By 
this we mean that though the " cause" assigned might produce 
some anaemia, it was not sufficient to produce this fatal anaemia 
and has presumably little or no connection with it. " Primary" 
means not the absence of any cause of anaemia in the history, 
but the absence of any sufficient cause so far as is known. 

xln attack of tertian malaria or a history of bleeding piles does 
not cause fatal anaemia in 999 out of 1,000 people who have such 
a history. In the 1000th it is a case oipost hoc and not propter 
hoc. Given the unknown cause that does lead to " primary" an- 
aemia, and it might be that a pregnancy or the presence of in- 
testinal parasites would act as the straw that breaks the camel's 
back; but tlie important causal factor is the imk'noicn factor. 
It is, then, by their etiology and not by their symptoms or by 
the blood examination alone that we distinguish primary from 
secondary anaemia. 

It is true that in the majority of cases we can tell from the 
blood examination alone whether a case is without known cause 



ANEMIA AND HYDREMIA. 



71 



(= "primary") or symptomatic (= "secondary"). But there 
appear to be enougli exceptions to this rule to make us cautious 
about stating it as a law. 



I. First Stage. — I defined anaemia above as a diminution in 
corpuscle substance. In the milder types of this condition the 
number of red corpuscles is not diminished at all, but the indi- 
vidual cell is small, pale, and of light weight, through loss of 
nitrogenous matter. This is appreciated : 

(a) As a lack of coloring matter; 

(h) As a lowering of the specific gravity. 

In the mildest grades of secondary anaemia there are no 
further changes. Such cases are those due to errors in hygiene 
— bad air, poor food, lack of light or exercise — to small hem- 
orrhages, and to the earlier stages of the diseases next to be 
mentioned. 

The lack of coloring matter is usually not present in every 
cell, as is seen in the stained specimens. Some are very pale at 
the centre, while others are well stained. 

n. Second Stage. — Usually the next changes to appear are, 
like those already mentioned, qualitative, the number of red cells 
still remaining normal or approximately so. 

The individual cell as seen in fresh preparations is more or 
less deformed and varies from its normal diameter, dwarfed 
forms usually being commoner than the giant forms. These 
variations in size and shape are sometimes termed "poiMlocij- 
tosis/' and the dwarf and gianl^ forms are called respectively 
microcytes and macrocytes. 

Maragliano ' has included the above changes, together with 
others about to be described, under the heading of 

Xecrohiosis in the red corpuscles, attributing them to a patho- 
logical condition of the serum. 

The changes united under this heading may be divided for 
convenience' sake into: 

(a) Endoglobular changes. 

iXI. Cong. f. lun. Med., Leipzig, 1892. 



! Primary = 
[ Secondary. 



Chlorosis, 

Pernicious anaemia, 



To be discussed under 
Special Pathology of 
the Blood, Chapter 
VII. 



Secondary Ancemia. 



72 



CLINICAL BLOOD EXAMINATION. 



(b) Poikylocytosis and crenation. 

(c) Changes in staining properties. 

(d) Changes involving motility in the corpuscle as a whole, 
or in parts of it. 

(e) Decrease in the average diameter of corpuscles with loss 
of the power to form rouleaux. 

All these changes may be watched in normal blood outside 
the vessels, as necrosis gradually comes on from contact with the 
air. Under pathological conditions the same changes may 



change their shape rapidly and continually; in dried and 
stained specimens they appear as sharply outlined light spaces 
in the corpuscle. In normal blood these changes occur after 
thirty to seventy minutes outside the vessels. In some patho- 
logical conditions specimens show them the instant the blood 
is collected, and presumably they were present before it left the 
vessels. 

(h) Crenation and Foikilocytosi s (Fig. 18, 6). — What we 
ordinarily know as crenation in the corpuscles is the same sort 
of process which, occuring within the vessels, we call poikilocy- 
tosis. A lump rises at one or more points in the corpuscle, 
becomes more pointed, and gradually the whole cell acquires 
amoeboid motions, assuming in succession the various shapes 
with which we are familiar in poikylocytes. 

(c) The pointed projections may break off and move about 
actively in the plasma. These motions, as well as the preceding. 




occur outside the body, but 
more quickly than usual 
(as other diseased tissues 
decompose more quickly 
after death than those of 
a sound man suddenly 
killed), or inside the body. 



Fig. 18. —Degenerative Changes in Eed Cells. 



{a) Endoglobular Changes 
(see Fig. 18, a), — These 
consist in the appearance 
of clear hyaline spaces of 
various shapes within the 
corpuscle, round, triangu- 
lar, rod-shaped, etc. In 
the fresh specimen they 



ANJEMIA AND HYDRJEMIA. 



73 



amoeboid movement of the whole corpuscle, are to be explained 
as irregular contractions of the necrobiotic protoplasm, similar 
in a general way to the actions of a hen after its head is cut off. 
These motions are not to be confounded with the finer Brownian 
or " molecular" movement to be seen in any healthy cell. The 
small bits broken off (Fig. 18, c) are doubtless the dwarf cells 
seen in dried and stained preparations. Curiously enough, 
these fragments tend again to assume the biconcavity character- 
istic of normal cells, as a drop of fat breaks into smaller but 
similar drops. 

(d) Changes in Staining Properties. — Normal red corpuscles 
have affinity only for acid stains (eosin). The same degenera- 
tive changes that lead to the alterations in shape and size above 
described alter the staining properties of the cell as well, so 
that it takes up two or three colors (according to the number 
present in the stain), either as a diffuse mixture or irregularly, 
some parts of the cell taking color differently^ from others. This 
has been termed a " polychromatophilic'' or degenerative change. 
Some observers have supposed it to be rather of the nature of 
regeneration, believing that the cells take color in this unortho- 
dox way because they are half-developed, but the weight of evi- 
dence is that they are degenerative changes. 

(e) In many secondary anaemias, especially in those asso- 
ciated with inflammations, the average diameter of the cells is 
lessened, and the rouleaux are not formed.' 

(/) Cells may lose their haemoglobin altogether, leaving 
only the shell of the corpuscle behind (see Fig. 18, d). 

Now all these necrobiotic changes are characteristic of the 
severer grades of secondary anaemia such as occur in cancerous 
cachexia, phthisis, nephritis, etc. 

The changes of staining affmity are less common than the 
otheTs, and usually represent the severest grades of anaemia, but 
they have also been noted occasionally in smallpox, measles, 
scarlet fever, typhus, and purpura. 

In pernicious anaemia they are, as a rule, much more common 
than in any other disease. Maragliano considers these degener- 
ative changes to be due to toxic plasma. A lessened resistance 
to the ordinary plasma-environment on the part of the red cells 

' But in the severest forms of angemia the diameters are apt to be in- 
creased (see below, Pernicious Anaemia). 



74 



CLINICAL BLOOD EXAMINATION. 



would also explain tliem, and in such affections as paroxysmal 
lisemoglobinuria it seems the most probable cause. In syphilis 
the abnormal sensitiveness of the red cells to the influence of 
mercury seems another instance where the red cells are imma- 
ture, decrepit, or weak. In syphilitic children, for instance, 
mercury easily gives anaemia, while in healthy children it does 
not. This will be discussed more fully under syphilis. 

The necrobiotic phenomena above described have been ob- 
served by Maragliano in carcinoma, lead poisoning, leukaemia, 
pernicious anaemia, purpura, cirrhotic liver, nephritis, pneu- 
monia, malaria, typhoid, erysipelas, and tuberculosis. Celli 
and Guarnieri (Fortschritte der Medicin, 1889, No. 14) found 
them in measles and scarlet fever. Weintraub (Firchoiv\s Ar- 
chie, Vol. 131) noted them in epilepsy, pyaemia, and catarrhal 
jaundice. 

A decreased resistance to pressure of electric currents and 
other influences has also been noted by v. Limbeck in some 
cases. 

Such weakening of the red cells experimentally produced in 
animals b}^ poisons has been found (My a and Sanarelli, Arch. 
itaL di Biolog., XYIL, 1892) to increase the susceptibility to 
infectious diseases. 

III. Third Stage. — Here the number as well as the quality 
of the red cells begins to suffer. So far I have mentioned only 
the qualitative changes in secondary anaemia and have purposel}^ 
made these changes more prominent than the actual diminution 
in the count of red cells, because it is only comparatively rarely 
and in very marked cases that the diminution in red corpuscles 
is considerable. The blood characteristic of most cases of sec- 
ondary anaemia is one in which the number of red cells is ap- 
proximately normal. 

The important exceptions to this rule are: 1. The anaemias 
of infancy and early childhood. 2. Large hemorrhages (soon 
after their occurrence). 3. Malaria. 4. Acute septicaemia. 

The direct and rapid destruction of the corpuscles by the 
malarial organism or hemorrhage account for this. Of sepsis 
and the anaemias of infancy we shall speak later. 

IV. Fourth Stage. — The blood of secondary anaemia shows 
often evidence not only of degeneration and destruction of the 
cells but also of regenerative changes, namelj^ : 



ANEMIA AND HYDREMIA. 



75 



Nucleated Bed Cells. 

These are usually divided into three groups 

(a) Normoblasts. 

(b) Megaloblasts. 

(c) Microblasts. 

Normohlasts. 

{a) The first are normally present in moderate number in the 
bone marrow of healthy persons, and in great numbers in the 
marrow after hemorrhage. They are generally considered to be 
a younger stage in the life of the corpuscle than the non- 
nucleated forms seen in the circulating blood. Hence the ap- 
pearance in the peripheral circulation of this form of nucleated 
cell is considered to mean that, in the comparatively plentiful 
rejjroduction of red cells called forth in the marrow by an 
anaemia, a certain number of red cells leave the nursery (the 
marrow) before they are grown up and circulate for a time in 
their immature state. A normoblast, then, represents an im- 
mature red corpuscle (see Plate IV.). 

In size and color it is like an ordinary red cell except that we 
find, usually somewhat to one side of it, a round nucleus about 
one-half the diameter of the whole cell. With the Ehrlich- 
Biondi tricolor mixture, this nucleus stains very deep blue, 
nearly black, and is sharply outlined against the pale yellow of 
the cell body round it. 

As the cell grows older it often pushes its nucleus out, and 
accordingly in many instances we actually see the nucleus pro- 
jecting over the edge of the corpuscle, or half out of it, and occa- 
sionally we find it l^dng beside the corpuscle from which it has 
just emerged.^ Not infrequently, of course, the cell lies so 
placed that this expulsion of the nucleus happens to be " up- 
ward," or toward the eye of the observer; in this case we 
notice that the nucleus is more or less out of focus when the cell 
body is in focus, and that when we draw up the lens a Uttle it 
becomes clearer. 

Very frequently the nucleus has toward the centre a light 
spot, sometimes so brilliant that it looks like the reflection of 

^ According to Ehiiich a new non-nucleated red cell is formed from 
this extruded nucleus. 



76 



CLINICAL BLOOD EXAMINATION. 



light from tlie surface of a drop of ink or any dark liquid, what 
a,rtists call the "high light." Occasionally there are several of 
these light spots in a nucleus, or it may be all light blue-gray ex- 
cept a dark blue rim. This is the commonest type of normo- 
blast. But now and then we meet with one when the nucleus 
is more or less separated into two or more pieces. These pieces 
are usually connected by pale-staining "bridges," perhaps ra- 
diating from a centre so that the nucleus is "rosette-shaped," 
or it may take any one of a large number of different shai:)es. 
The parts of the nucleus which are nearest the periphery of the 
cell usually stain deeper than the "bridges" which join them. 

Sometimes the nucleus breaks apart completely and we find 
two or more separate unconnected nuclei within the single cell.' 
Or one of the pieces may be outside the cell and the others inside. 

Earest of all is the appearance of true mitosis in the nucleus 
of a normoblast. 

^legcdohlasts. 

(h) The typical megaloblast as usually described is so unlike 
the normoblast that we should not natui-ally think of them as 
near relations. 

It does not occur anywhere in the healthy adult body, not 
even in the bone marrow. In the foetal marrow and in the 
marrow and circulating blood of very grave forms of anaemia it 
is to be found, usually in comjDany with a certain number of 
normoblasts. 

Ehrlich has described it as the sign or product of a wholly 
different type of blood formation, namely, the foetal type, and 
considers those anaemias in which it occurs as tending to a re- 
turn of the blood to the foetal state. Here the nucleus, instead 
of being extruded, is absorbed, and does not give rise to a new 
cell, so that there is no tendency to regeneration of the blood 
such as is expressed by the normoblast. Hence he regarded the 
presence of megaloblasts as a bad prognostic sign, and believes 
that a pernicious or fatal anaemia was characterized by aii excess 
of these ceUs over the normoblasts. He recognized that they 
might be found in various milder forms of anaemia ; but here the 
prevailing type is the normoblast, and regeneration may be more 
active than degeneration. 

The typical hiegaJohhst is an abnormally large cell (11 to 20 
' Apparently the nucleus is sometimes absorbed and not pushed out. 



PLATE IV. 



(a) In the "typical megaloblasts " {m,m,m,m) note the white line 
around the nucleus, the variations in its tint, and, in two of them, the 
discolorations of the protoplasm (polychromatophilia), especially near the 
nucleus. The lower of the two cells in karyokinesis shows this best. 

(b) Note in the cells with dividing nuclei {D,D,D,D) the grayish 
" bridges" joining the separate parts of the nuclei. 

(c) In the microhlast note the ragged edge of the protoplasm. 

{d) In the lower portion of the plate (" cells deformed in size or shape'') 
an actual field from a case of pernicious anaemia was copied. Macrocytes 
(or large cells), microcytes (or small cells), and misshapen cells or poikilo- 
cytes are shown. 

(e) The " polyehromatophiUc celW^ in the lower right-hand corner were 
stained with the same mixture as those to the left of them, but have taken 
up other colors besides the orange G, which alone is taken up by normal 
red cells. 



Examination of the Blood. 

PLATE IV. 




Varieties of Nucleated Red Cells. 

m. m. m. m.=TypicaI megaloblasts D. D. D. D =Cells with di^^d^ng nuclei 
o. 0. o. o. o. o. o. = Other (unnamed) varieties of nucleated red corpuscles. 



Scale of [X 



4.^ 



,' Polycliomatopliilic cells 
Cells deformed in size or shape 



R. C. Cabot fee. 



Lith. Anst. v. E. A. Funke, Leipzig. 



ANEMIA AND HYDREMIA. 



77 



in diameter, frequently showing marks of degeneration (poly- 
chromatophilia) in its protoplasm, which is therefore brownish 
or purplish with the Ehrlich-Biondi stain. Its nucleus is very 
large, filling most of the cell, and contrasts with the normoblast 
nucleus not only by its greater size but by the pale, even stain 
which it takes up. The commonest color of the nucleus with 
the Ehrlich-Biondi stain is pale green or robin' s-egg color. 
Sometimes it is not stained evenly but dotted over with purplish 
granules arranged in a mesh like the knots in a fish-net (see 
Plate lY.). 

Outside the nucleus there is usually a narrow band of clear 
white, apparently an empty space, separating the nucleus from 
the encircling protoplasm. The protofjlasm close round this 
colorless ring is usually stained more deeply than the rest of the 
cell. Cracks and " flaws" are sometimes to be seen in the proto- 
plasm, giving evidence, as its purplish stain does, of the necro- 
biotic changes described by Maragliano. 

The outline of the whole may be quite circular : oftener it is 
oval or somewhat irregular, but rarely much deformed. 

Microhlasts, 

(c) Microblasts, which are rarer than either of the varieties 
just described, consist of a nucleus like that of a normoblast or 
smaller, and contained in a cell body smaller than the normal 
red corpuscle. In the writer's experience the cell body is usu- 
ally reduced to a few shreds of discolored protoplasm hanging 
about the nucleus (see Plate lY.). Their significance is usually 
supposed to be that of megaloblasts. 

'^Atypical Forms.'' 

Unfortunately for our terminology and for Ehrlich's theory 
of two separate types of blood formation, we find in some cases a 
variety of other appearances in the nucleated red cells. Some- 
times we find in a given specimen of blood only typical normo- 
blasts, microblasts, and megaloblasts, and accordingly can easily 
reckon up the number of each kind and see which type of blood 
formation predominates. More often there are a few cells pres- 
ent, about the classification of which we cannot come to a deci- 
sion, and I have occasionally seen a specimen of blood contain- 
ing a large number of nucleated red cells no one of which could: 
6 



78 



CLINICAL BLOOD EXAMINATION. 



stricth' be classed either as a normoblast, a megaloblast, or a 
microblast, as these are usually defined. 

This I have attempted to illustrate in Plate IT. Judging 
from appearances Ave should naturally suppose these to be inter- 
mediate stages between the three types. Thus we find cells like 
some of those shown in Plate lY., which are like normoblasts 
excexjt that the nucleus stains pale green or even like a megalo- 
blast. The protoplasm of the normoblast very frequently shows 
a lesser degree of the degenerative changes supposed to be 
characteristic of the megaloblast. 

The other cells in the plate (o, o, o, etc.) illustrate other of 
these varieties. A list of those most commonly seen is as fol- 
lows : ' 

1. Cells like a normoblast, except in showing irregular out- 
line and degenerated protoplasm. 

2. Cells like a normoblast, except in having a pale green 
nucleus either small or nearly filling the cell. 

3. Combinations of the above. 

4. Cells like a normoblast, except that the dark nucleus fills 
nearly the whole cell. 

5. Cells like a normoblast, except that the cell body is as 
large as that of a megaloblast. 

6. Same as 5, but with pale nucleus. 

7. Cells like a megaloblast, but having a dark nucleus 
instead of a light one. 

8. Cells like a megaloblast, but showing only minute specks 
Df dark nuclear substance scattered through them. 

9. Cells like a normoblast with dividing nucleus, but much 
larger. 

10. Cells with mitosis in the nucleus. 

Besides the difficulties entailed by the existence of all these 
unnamed varieties, we have the ambiguity and uncertainty 
involved in the definition of the named types. For instance, 
a megaloblast is a cell considerably larger than a normoblast. 
How much larger? It has a large pale nucleus; how large and 
how pale? 

These questions may seem like quibbling, but when it 

^ I have seen all of these in a single cover-glass specimen, so that the 
differences do not depend on differences in the methods of preparation 
and staining. 



ANJEMIA AND HYDREMIA. 



79 



depends on the answer given to them whether we class a given 
cell as a megaloblast or as a normoblast, and the prognosis of 
the case depends on the relative proportions of these two varie- 
ties, it may make considerable difference which way we decide. ' 

For reasons given more fully in the chapter on " Pernicious 
Anaemia," I have usually adopted the following definitions: 

Normoblast : A nucleated red cell not over 10 /j- in diameter, 
whose nucleus is not more than one-half the diameter of the cell. 
The nucleus may he dividing or divided, hut must stain deeply. 

Megalohlast: All other varieties of nucleated red cells except 
microblasts. 

I think it is evident that there is no sharp line to be drawn 
between the three types of cells, or the two methods of blood 
formation, so that these divisions into normoblast, microblast, 
and megaloblast are somewhat misleading and arbitrary. But 
they have a certain convenience if used only to mean the 
extremes of the series, from the most fruitful to the least fruit- 
ful kind of nucleated cell. 

In secondary angemia of all kinds we maj always find 
normoblasts. In very severe forms, whatever the cause, we may 
or may not find an occasional megaloblast. But these are 
much rarer than the normoblasts, even in the severest types of 
secondary anaemia. The only exceptions to this rule are the 
anaemias due to intestinal parasites, in which, though secondary 
and curable, the megaloblasts in some cases predominate over 
the normoblasts. 

Summing up the changes characteristic of secondary 
anaemia, which includes almost all the important pathological 
appearances occurring in red cells, we have : 

( (a) Lack of haemoglobin. ) 

I. < (h) Lowered specific [ Characteristic of mild cases. 
( gravity. ; 

II. The above and necrobiotic ) Characteristic of moderate 

changes of Maragliano. f cases, 
f (a) Lack of red cells. ^ 
ITT J Presence of uormo- [^Characteristic of severe 
] blasts and the above [ cases. 

L (LandIL). J 

IV. Megaloblasts and the above ) Characteristic of very se- 
(I., II., and III.). f vere cases. 

' Cf. Askanazy : Zeit. f. klin. Med., 1896, vol. xxvii. 



80 



CLINICAL BLOOD EXAMINATION. 



The changes in the wliite cells will be discussed in the next 
chapter. 

Among the commonest causes of secondary anaemia are : I. 
Infective and febrile diseases, acute or chronic. II. Malignant 
disease. III. Chronic suppurations, nephritis, chronic dysen- 
tery, cirrhosis of the liver. lY. Bad hygiene, pregnancy, and 
lactation. V. Intestinal parasites. VI. Poisons (lead, arsenic, 
etc.). 

To discuss the way in which each of these influences acts 
in producing anaemia is tempting, but falls outside the plan of 
this book. 

2. Hydejemia. 

(a) Seen from the opposite point of view almost all cases of 
anaemia are hydraemic. That is, if the total volume of blood 
is to remain approximately constant (as it appears to do), any 
loss of solids (corpuscle substance) must be made up by water 
taken in from the tissues. Hence any anaemic person's blood 
is thin, watery, or hydraemic. Women's blood is somewhat 
more hydraemic than men's, because less rich in cells. 

(6) In many conditions of dropsy, whether from heart or 
kidnej', we ma}" have more water than normal, both in the 
plasma and in the corpuscles themselves, which are capable of 
taking up considerably more than their normal amount of 
water. 

(c) Any temporary dilution of the blood under the condi- 
tions mentioned above (ingestion of liquid, lowered blood pres- 
sure, etc.) is from one point of view" a hydraemic condition. 

No special clinical significance attaches to it other than 
that of anaemia, whose correlative it is. 



CHAPTER YIII. 



LEUCOCYTOSIS— LYMPHOCYTOSIS— EOSINOPHILIA— 
MYELOCYTES. 

Much confusion has been caused in the past by the failure 
to see in leuksemic blood anything more than an extreme and 
permanent form of leucocytosis, while leucocytosis was thought 
of as a mild and temporary leukaemia. 

We know now that they are totally different phenomena, 
differing not in the number, but in the hind of cells present in 
the increased numbers. 

Definition. 

There are many difficulties in defining leucocytosis. To my 
mind the term is best used to mean: An increase in the nitmber 
of leucocytes in the imdplieral blood over the number normal in the 
individual case, this ina^ease never involving a diminution in the 
polymorphonuclear varieties, but generally a marked absolute and 
relative gain over the number previously present. 

(a) I say "in the peripheral blood" because the majority of 
observers now hold that leucocytosis is not a real increase in 
the total number of leucocytes in the blood, but only an affair 
of distribution, the cells being drawn or attracted to the pe- 
riphery and out of the internal organs. Whether this theory 
be true or not, it is accurate to say that in the drop which we 
draw (whether also in the internal organs or not), the leuco- 
cytes are present in increased numbers per cubic millimetre. 

(b) In persons not usually to be considered sick, but simplj^ 
somewhat wizened or ill-nourished, the normal count of white 
cells may be as low as three thousand per cubic millimetre. 
For such an individual ten thousand cells per cubic millimetre 
would be a decidedly pathological condition. On the other 
hand, there are persons, usually those of notable vigor and 
good nutrition, whose white cells rarely fall below ten thousand. 

Obviously we must take account of these differences both in 
our definition and in our practice if we are to reason correctly 
from the data of blood examination. 



82 



CLINICAL BLOOD EXAMINATION. 



(c) Further we must lay stress upon tlie varieties of leuco- 
cytes whose increase constitutes leucocytosis in distinction from 
either variety of leukaemia (sx-)lenic-myelogenous, or lymphatic). 

For instance, given a count of eighty thousand leucocytes 
per cubic millimetre, we cannot tell without knowing the va- 
rieties of cells present whether the case is a genuine leukaemia 
or a merely leucocytosis symi)tomatic of pneumonia, suppura- 
tion, malignant disease, or other conditions. 

(d) Thus defined leucocytosis is of two kinds. 1. That in 
which the relative proportions of the different varieties to each 
other is unchanged. 2. That in which the increase is made up 
solely or largely by a. gain in the polymorphonuclear or adult 
leucocytes. 

The latter includes nearly all pathological leucocytoses, the 
former being confined chiefly to the physiological leucocytoses 
next to be described. 

(e) Lastly, in order to be sure that the i^olymorphonuclear 
cells are not decreased, we must know what the normal iDercent- 
age for iliat uidii'idwjl is. The normal percentage of these cells 
in infancy is from twenty-eight to forty per cent. In adults it 
is much higher, but varies like the total county according to 
conditions of nutrition, etc. Thus the normal for adults is 
usually set at from sixty to seventy per cent, but no one indi- 
vidual's blood shows such variations in health, and if we 
include the obviously ill-nourished, but not actually sick, and 
also those in blooming health, we shall have to widen our nor- 
mal limits considerably. From fifty to seventy-five per cent 
are vrithin normal limits according to the above conception. 
But obviously we can make no absolute judgment by a standard 
so vague. It is much better, I think, to consider each indi- 
\idual as his own standard within these limits, his count of 
polymorphonuclear cells being a fair measure of the soundness 
and vigor of his metabolism. Thus, in an obviously debilitated 
individual, we should consider seventy -two per cent of these 
cells very high, while in a vigorous athlete it might not be so. 

It is the endeavor to include all these limiting conditions 
that has made my clefixiition so long and involved. It gives us, 
if it turns out to be true, some better way of classing individuals 
than as "sick" or "well" as regards their blood state. "We find 
out lioio well or how sick their blood is (to a certain extent), (a) 



LEUCOCYTOSIS. 



83 



by tlie total number of leucocytes present, and (b) by the pro- 
portion of old cells (polymorplionnclear) in a given one thou- 
sand of those leucocytes. These data tell us approximately Jioiv 
normal or Jiow abnormal a given individual's blood is. When a 
given disease like pneumonia occurs, we need to know, if pos- 
sible, what is the ordinary leucocyte count and differential 
count of that case, on top of which a leucocytosis may (or may 
not) be built up. 

Condition of stasis, temporary blood concentration, dilutioUy 
and vasomotor disturbances must, of course, be excluded or 
allowed for, since these may increase not only the total leucocyte 
count, but often the percentage of adult cells. "WTietlier or not 
differences of race make any difference in the normal count of 
white cells, I cannot say, but certainly the average of a group of 
college athletes would be higher than that of some country towns 
in New England where everybody is more or less under-nour- 
ished; and if one is to practise among all sorts and conditions 
of men, I think he cannot but expect to find people's leucocytes 
vary all the way /ro??i 3,000 to 10,500 per cnlnc miJUmetre, with- 
out there being anything more than malnutrition to account for 
the lower figures. 

Into the theories of how leucocytosis is brought about I 
shall not enter ; no one of them as yet commands general assent. 

We may di^^.de leucocytoses for convenience' sake into : 1. 
Physiological leucocytoses. 2. Pathological leucocytoses. 

Physiological Leucocytoses. 

1. Leucocytosis of the new-born. 

2. Leucocytosis of digestion. 

3. Leucocytosis of pregnancy. 

4. Leucocytosis of post-partum. 

5. Leucocytosis after violent exercise, massage, and cold 
baths. 

6. Leucocytosis of the moribund state. 

The Leucocytosis as Affected hij Digestion. 

(a) Total abstinence from food lowers the leucocyte count. 
In the blood of the professional faster Succi, the number sank 
within his first week's fast to 861 per cubic millimetre. After 



84 



CLINICAL BLOOD EXAMINATION. 



the first week it rose to 1,530, and remained there throughout 
his thirty days' abstinence (Luciani '). 

Yon Limbeck counted the blood of a melancholic patient 
who had fasted a week, and found 2,800 white cells per cubic 
millimetre. These facts support the idea that the number of 
leucocytes depends (within certain limits) on the individual's 
assimilation of food. In cancer of the gullet we fijid similar 
low figures. 

{h) After a meal rich in proteids the leucocyte count rises 
about thirty -three per cent in most sound persons. Ten thou- 
sand cells may perhaps be considered the average, three to four 
hours after a proteid meal, but if the count before a meal is 
only 4,000 or 5,000, digestion will i)erhaps not raise it above 
7,000, while vigorous adults may show 13,000. Digestion leu- 
cocytosis is always relative to the count of the individual's 
blood luJien fasting. This is to be obtained preferably before 
breakfast, as during the day the leucocytosis caused by one meal 
may not be gone before the influence of the next meal begins. 

Occasionally we see sound persons with little or no digestive 
leucocytosis. Some of these cases are to be explained by habit- 
ual constipation (v. Limbeck) ; in others the reason is more 
obscure. But there is no doubt of its being the rule after 
meals of mixed or proteid diet. In herbivorous animals, and 
presumabh^ in vegetarians, it is not found. 

Any disease of the gastro-intestinal tract, whether functional 
or organic, may prevent the appearance of the digestion leuco- 
cytosis (see later under Diseases of the stomach, page 241). In 
angemic and debilitated conditions it is frequently absent. 

In children it is especially marked. Schiff ^ records a case 
of a healthy infant whose blood an hour after birth showed 
19,500 (see next section), after its first meal 27,625, and after its 
fourth meal 36,000 white cells per cubic millimetre. After the 
second day this gradually diminished. 

Food seems to call forth a greater leucocytosis in proportion 
as it is a novelty in the stomach. Cases of gastric ulcer who 
had been fed exclusively by rectum for some weeks show a 
greater leucocytosis after their first meal than later. Perhaps 
the size of the digestion leucocytosis in the new-born is to be 

^ "Des Hungern, " German translation by O. Frankel. Hamburg, 1890. 
2Zeit. f. Heilk., xi., 1890. 



LEUCOCYTOSIS. 85 

similarly explained. In diabetics the digestion leucocytosis is 
sometimes very large. 

The leucocytosis can usually be observed one hour after a 
meal, increases for two, three, or even five hours according to the 
slowness of digestion, then falls again. 

Excepting the eosinophiles, the proportion of the different 
varieties of leucocytes to each other is not considerably affected, 
this being one of the few varieties of leucocytosis in which the 
increase takes place "all along the line," without special pre- 
dominance of any single variety. In other words, the blood is 
neither older nor younger. The eosinophiles, however, are 
markedly diminished. 

Diagnostic Value. 

1. When we wish to know whether a person is accurate in such 
statements as that they have " eaten nothing for a week," we can 
get evidence from the leucocyte count, which should be very low 
if the assertion be true. Whenever we cannot communicate 
with a patient and wish to know how much food he has taken of 
late, we can form some idea from the blood examination. In 
the case of a patient who spoke only Russian, I was led to 
look for a stenosis of the gullet by the lowness of the leucocyte 
count (2,700), and the probang confirmed the suspicion. 

2. As suggested above, we can form some idea of a jjerson's 
general vigor, nutrition, and capacity to assimilate food by the 
number of leucocytes and the proportion of mononuclear 
(young) cells, as compared with the average figures for that age 
and locality. Persons debilitated from anj^ reason are apt to 
show it in their blood by the changes above mentioned, the 
element of hysteria being sometimes recognizable by other 
signs (see below: " Eosinophilia, " page 101). 

3. Slowness of digestion is indicated by a late apjjearance of 
the digestion leucocytosis. The inferences to be drawn from the 
blood in diseases of the gastro-iutestinal tract will be discussed 
later (page 236). 

4. Perhaps the chief importance of digestion leucocytosis is 
as a possible cause of false inferences, through being taken for a 
pathological increase. Bearing this in mind, we must always 
examine the blood as near a meal as possible, or better still 
before breakfast. 



86 



CLINICAL BLOOD EXAMINATION. 



Leucocytosis of the New-Born. 

The following table is compiled from the best authorities on 
the subject (Schiff, Gundobin, Bayer, Hayem, and others) : 



Age. 



At birth 

End of first day 

" second day 

" fourth day 

" seventh day 

Tenth day 

Twelfth to eighteenth day 

Sixth month 

Sixth year and upward . . . 



Red cells. 



5,900,000 



7,000,000 to 8,800,000 
Generally increased. 

6,000,000 

5,000,000 



Leucocytes. 



17,000 to 21,000(26,- 
000 to 36, 000 after 
first feeding) . 
24, 000 
30, 000 
20,000 
15,000 
10,000 to 14,000 
12,000 
12,000 
7,500 • 



The increase is explained by Lepine, v. Limbeck, and others 
as a combination of blood concentration with large digestion 
leucocytosis. Gundobin and others are opposed to this theory. 
Certainly the influence of digestion on infant's blood is much 
greater than in adults. After a meal 30,000 leucocytes is never 
a very high count in infants under two j-ears. 

A fuller discussion of the subject will be found in the chapter 
on the blood in infancy. 



TJie Leucocytosis of Pregmmcy. 

Most primiparce sJiow during the latter months of pregnancy a 
moderate increase of aU varieties of leucocytes. Thirteen thou- 
sand cells per cubic centimetre is about the average count. 

In multiparae it occurs in only about fifty per cent of the 
cases. Digestion leucocytosis "on top of" the constant preg- 
nancy leucocytosis, so to speak, does not occur. 

As mentioned above, the relative percentage of the different 
types of leucocyte remains unchanged, so that all varieties must 
be equally increased (eosinophiles excepted). The fact that 
digestion does not increase the pregnancy leucocytosis, leads 
to the suggestion that the whole thing may be only a prolonged 
digestion leucocytosis — the mother having to eat for two. The 
swelling of the breasts may also account for part of the leuco- 



LEUCOCYTOSIS. 



87 



cytosis. In the last weeks of pregnancy the leucocytosis 
increases till at the beginning of labor it is often 16,000 to 
18,000. It has no diagnostic value, as it is not present during 
the earlier months of pregnancy when diagnosis is difficult, and 
in the later months such conditions as hydatiform mole and 
fibroid tumors might raise the count of white cells as much as 
pregnancy. 

Leucocytosis After Parturition. 

The following charts illustrate the course of the leucocyte 
curve from the time of parturition till the end of the second week 
after it. 

All were primiparae excepting Nos. 5, 8, and 9. There was 
no sepsis in any case, and the temperature charts were practi- 
cally normal after the second day. No reasons are known for 
the variations between the different cases. All were counted at 
the same hour of the day, and under the same conditions of 
nutrition. All nursed their children. 

The only importance of this leucocytosis is that it might be 
confounded with a pathological leucocytosis in a case suspected 
of being septic. Just how long the leucocytosis is prolonged 
during lactation has not been studied so far as I am aware, but 
it certainly may go on several weeks. 

Violent exercise, massage, and short cold hatJis have been 
shown to cause a temporary increase in the number of leuco- 
cytes in the peripheral blood, all varieties of the cell being equally 
increased. The explanation usually given is that the blood 
is concentrated by vasomotor contraction and rise of blood 
pressure. 

Schultz {Deut. Arcli. f. Min. 3Ied. , 1893, page 234) found the 
leucocytosis of exercise amount to about the same as that of 
digestion, 11,000 to 13,000. He also noted that in dogs 
merely opening the peritoneum aseptically or breaking a leg 
caused leucocytosis. 

Thayer studied twenty cases of typhoid and found an aver- 
age of 7,724 white cells before and 13,170 after a Brand bath 
{Johns Hophins Medical Bidletin, April, 1893). The increase 
took place equally in all varieties. Winternitz (Imperio-Eoyal 
Medical Society, Yienna, February, 1893) came to a similar 
conclusion and found also that prolonged cold bathing decreased 



88 



CLINICAL BLOOD EXAMINATION. 



the number of white cells (dry cold does the same). On the 
contrary, short hot baths decrease and prolonged ones increase 
the number of leucocytes. 




m 



i 



^ a 
a- a 



2 33 

3 3 




cS o 
o o 



Local arm baths have a similar effect, raising the count of 
leucocytes in the blood of the immersed arm if cold and short, and 
lowering it if hot and short, while prolonged immersion has an 



LEUCOCYTOSIS. 



89 



opposite effect. In the otlier arm tlie counts go up when those of 
the immersed arm go down, and vice versa (Rovighi) . ' Mitchell 
found that the leucocytes showed distinct increase (as well as the 
red cells and haemoglobin) after one hour's general massage. 





























































































































































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1 









o £ 



All these forms of leucocytosis are usually explained by 
changes in blood pressure, and vasomotor changes affecting the 

1 Arch. Ital. d. Clin. Med., xxxii., 3, 1893. 

2 American Journal of the Medical Sciences, May, 1894. 



90 



CLINICAL BLOOD EXAMINATION. 



calibre of the peripheral vessels and consequently their con- 
tents. 

Terminal Leiicocytosis. 

The leucocytosis of the moribund state, though by no means 
invariable, occurs in many cases, whether from the influence of 
a terminal infection or from stasis. Where death is sudden or 
rapid it does not occur. It seems to be analogous to the ter- 
minal rise of temperature seen at the close of many chronic 
non-febrile affections. The longer the patient is moribund the 
higher the count reaches. In pernicious anaemia the increase 
may be so great as to simulate lymphatic leukaemia. Such a 
case occurred in the writer's own experience. The patient had 
presented the signs and symptoms of pernicious anaemia, and 
the blood was typical of the disease in all respects except for 
the lack of nucleated red cells. 

Slides taken on the day of death showed a ratio of one white 
to fifteen red cells, the small lymphocytes greatly predominat- 
ing, but the autopsy revealed simply the lesions of pernicious 
anaemia. The differential count of one thousand leucocytes on 
the day of death showed : Young cells, 91.7 per cent ; adult cells, 
7.7 per cent; old cells, 0.5 per cent. Four megaloblasts were 
seen while counting these. The total leucocyte count was un- 
fortunately not made. 

In ordinary cases the differential count shows an increase 
in the adult leucocytes. Thus in a case reported by Rieder, 
in which the leucocyte count rose during the last two days of 
life from 7,800 to 59,300, the polymorphonuclear cells consti- 
tuted 87.5 per cent of the whole 59,300. 

Pathological Leucocytoses. 

For convenience' sake these may be divided as follows : 

1. Post-liemorrhagic leucocytosis. 

2. Inflammatory leucocytosis. 

3. Toxic leucocytosis. 

4. Leucocytosis in malignant disease. 

5. Leucocytosis due to therapeutic and experimental in- 
fluences. 



PATHOLOGICAL LEUCOCYTOSIS. 



91 



1. Post-JiemorrJmgic Leucocytosis. 

Within an hour after a large hemorrhage we find commonh^ a 
considerable increase (16,000-18,000). In hemorrhage from the 
stomach this disappears again usually within a day or two, 
while in ordinary traumatic hemorrhage it persists longer. 
This last fact may perhaps be explained, as v. Limbeck sug- 
gests, by the local conditions in the wound rather than by the 
loss of blood in itself. 

The adult leucocytes are increased relatively and absolutely 
as in other forms of pathological leucocytosis. The degree of 
increase in the white cells is parallel in a general way to the 
ansemia produced in the individual, i.e., it depends on his pow- 
ers of recuperation rather than on the amount of blood lost. Its 
duration follows the same rule.* 

2. Inflammatory Leucocytosis. 

I use the term "inflammatory leucocytosis" rather than 
"leucocytosis of infectious diseases" because there is a consider- 
able number of infectious diseases in which no leucocytosis oc- 
curs, while it accompanies almost all forms and cases of inflam- 
mation. Nevertheless I shall class under this heading some 
diseases in which inflammation plays but a very subordinate 
role. 

I. Although 2Jurident and gangrenous processes usually cause 
a higher count of white cells than serous processes, the amount 
of the exudation is not a measure of the amount of leucocytosis. 
It seems to depend rather on the resultant of two forces, viz., 
the severity of the infection and the resisting power of the indi- 
vidual. These factors may interact in various ways : 

1. Infection mild : resistance good = small leucocytosis. 

2. " less mild : " less good = moderate leucocytosis. 

3. " severe: " good = very marked leucocytosis. 

4. " " " poor = no leucocytosis. 

This will be illustrated later under "Pneumonia" and under 
"Sepsis." Experiments on animals show that whereas moder- 
ate sized doses of septic cultures, not sufficient to kill the 

^ Further account of the blood after hemorrhage will be found on page 
109 et seq. 



92 



CLINICAL BLOOD EXAMINATION. 



animal, are followed by leucocytosis, larger doses after which 
death follows speedily, do not raise the leucocyte count at all. 
Animals weakened hj any cause show less leucocytosis to a 
moderate dose than strong animals. 

If the individual reacts from the shock his leucocytes are in- 
creased again and rise above normal. If reaction fails the leu- 
cocytes do not rise. 

II. Inflammatory leucocytoses differ from physiological leu- 
cocytoses — 

(a) In being usually of larger extent. 

(b) In being accompanied by a relative and absolute increase 
in the percentage of polymorphonuclear (adult) cells. 

III. The course of the leucocytosis as regards both amount 
and duration shows, like the temperature chart, certain more or 
less characteristic differences in different diseases. 

lY. In some cases in which the absolute number of leuco- 
cytes is not increased, we see a relative increase in the adult 
cells, pointing to the fact that influences are at work similar to 
those which produce an absolute increase. 

Y. That the amount of exudation is not of itself a measure of 
the amount of leucocytosis is shown by the fact that erysipelas 
or scarlet fever may be accompanied by as high a count as the 
average count in pneumonia or empyema. 

That purulent exudations usually have more effect on the 
white cells than do serous ones is due, I suppose, to the fact 
that a purulent inflammation usually means a severer infection. 

YI. No direct connection exists between leucocytosis and 
fever, many febrile affections running their course with a normal 
leucocyte count. When both leucocytosis and fever are due to 
the same causes they rise and fall together, but the correspond- 
ence is rarely accurate, and marked leucocytosis may exist with- 
out fever. 

YII. Acute, rapidly spreading inflammations seem to pro- 
duce a greater leucocytosis (other things being equal) than 
those in which the process is relatively chronic and stationary. 
For instance, an appendicitis, when well w^alled off and station- 
ary, shows less increase in white blood cells than while its le- 
sions are progressing. But peracute, overwhelming general sep- 
sis may have no effect on the leucocytes, the reactive power of 
the organism being crushed. 



PATHOLOGICAL LEUCOCYTOSIS. 



93 



YIII. Most inflammatory leucocytose^ are preceded by a 
temporary diminution in the number of leucocytes. This oc- 
curs in animals from shock of any kind (blows on the head, 
tying to the etherizing board), and it seems not unlikely that 
the cause is the same in all cases. 

The following is a list of the more important inflammatory 
or infectious conditions in which leucocytosis appears : 

1. Infectious diseases ivitli comjjaratively slight local infiamma^ 
tory processes : 

(a) Asiatic cholera. 

(6) Relapsing fever. 

(c) Typhus fever (according to the majority of observers). 

(d) Scarlet fever. 

(e) Diphtheria and follicular tonsillitis. 
(/) Syphilis (secondary stage). 

(g) Erysipelas. 

{h) The bubonic plague. 

2. Infectious diseases with more extensive local lesions : 
(a) Pneumonia. 

(6) Small-pox (suppurative stage). 

(c) Malignant endocarditis, puerperal septicaemia, and all 
pysemic and septicsemic conditions. 

(d) Actinomycosis. 

(e) Trichinosis. 
(/) Glanders. 

(g) Acute multiple neuritis and beri-beri. 

(h) Acute articular rheumatism. 

(^) Septic meningitis and cerebro-spinal meningitis. 
(j) Cholangitis, cholecystitis, and empyema of the gall blad- 
der, i 
(k) Acute pancreatitis. 

(1) Endometritis, cystitis (some acute cases). 
(m) Gonorrhoea. 

3. Local inflammatory processes : 

(a) Abscesses of all kinds and situations, such as 

Felon. 

Carbuncle, furunculosis. 

Tonsillar and retropharyngeal abscess. 

Appendicitis. 

Pyonephrosis, perinephritic abscess and pyelonephritis. 
7 



94 



CLINICAL BLOOD EXAMINATION. 



Osteomyelitis. 

Psoas and hip abscess when not simply tubercular. 
Abscess of lung, liver, spleen, ovary, prostate. 
Salpingitis and pelvic peritonitis. 

(b) Inflammatioris of the serous membranes including : 
Pericarditis, peritonitis, pleurisy, arthritis (serous or puru- 
lent, non-tubercular). 

(c) Gangrenous inflammations, as of the 
Appendix, lung, bowel, mouth (noma). 

{d) Many inflammatory skin diseases, such as dermatitis, 
pemphigus, pellagra, herpes zoster, prurigo, some cases of uni- 
versal eczema, etc. 

3. Toxic Leucocytosis. 

Under this heading I have grouped most of the conditions 
not obviously to be explained as infectious or inflammatory 
(though some may turn out to be such) and not due to malig- 
nant disease or therapeutic agencies. This classification is 
chiefly for convenience' sake and represents only a guess at the 
real explanation of the leucocytosis : 

(a) Leucocytosis of illuminating-gas poisoning. 



(&) 


u 


" quinine poisoning. 


(c) 


a 


" rickets (many cases). 


{d) 


u 


" the uric-acid diathesis, gout. 


ie) 


(C 


" acute yellow atrophy of the liver. 


(/) 


u 


" advanced cirrhosis of the liver (some 






cases) especially with jaundice. 


(9) 


K 


" acute gastro-intestinal disorders (pto- 






mains ?) . 


(h) 


K 


" acute nephritis, and some chronic cases, 






usually ursemic. 


<i) 


U 


" hydronephrosis. 


(J) 


a 


after injections of tuberculin and thyroid 






extract. 


Qc) 


u 


after injection of normal salt solution (in- 






travenous) . 


il) 


(( 


after ingestion of salicylates. 


(m) 


u 


during and after etherization. 


Possibly the leucocytosis of acute delirium belongs also in 


this group. 







PATHOLOGICAL LEUCOCYTOSIS. 



95 



4. Leucocytosis of Malignant Disease. 

Yery likely this belongs more properly under one or another 
of the classes just mentioned. Some observers think that it oc- 
curs only from the inflammation excited in the periphery of 
some malignant tumors ; others that it is due to absorption of 
morbid products from the tumor itself ; others again that it is 
to be accounted for by the cachectic state associated with the 
growth of the tumors. The details and conditions of its occur- 
rence will be discussed later (page 287). 

5. Leucocytosis Due to Therapeutic and Experimental Influences. 

Pohl ' found that most of the so-called tonics and stomachics 
produce a slight increase in the white cells in animals, particu- 
larly the vegetable tonics like tincture of gentian, and oil of 
anise seed, while bismuth, bicarbonate of soda, and iron had no 
such effect. Quinine, caffeine, and ethyl alcohol gave likewise 
negative results. Yon Limbeck found leucocytosis in men after 
oil of peppermint and oil of anise seed. 

Binz ' got the same results with camphor. In all these ex- 
periments the substances were given by the mouth. 

Using subcutaneous or intravenous injections, Lowit exjieri- 
mented on animals with hemialbumose, peptone, pepsin, nucle- 
inic acid, nuclein, extract of blood-leech, pyocyanin, tuberculin, 
curare, uric acid, urate of sodium, and urea. All but the last 
of these produce temporary decrease followed by increase of 
leucocytes. 

Goldschneider and Jacob ^ used extracts of various organs. 
Extract of spleen, marrow, and thymus produced leucocytosis 
preceded, as in Lowit' s experiments, by a brief diminution in 
the number of leucocytes, while extract of pancreas, thyroid, 
kidney, and liver had no effect. 

Winternitz * injected a large variety of substances silbcutane- 
ously and found that the degree of leucocytosis was parallel to 
the degree of local reaction excited. 

For example, neutral salts and weak acids or alkalies pro- 

'Arch. f. exp. Path. u. Pharm., 1889, vol. xv. 

2 Arch. f. exp. Path. u. Pharm., vol. v., p. 122. 

3 Arch. f. Anat. u. Physiol., 1893, p. 567. 
*Arch. f. exp. Path. u. Pharm., vol. xxxv., p. 77. 



96 



CLINICAL BLOOD EXAMINATION. 



duced slight local inflammation and a leucocytosis of from forty 
to seventy-five per cent of the original count. But irritants like 
turpentine, croton oil, nitrate of silver, sulphate of cojjj^er, 
mercury, antimony, digitoxin, etc., produced local suppuration 
(aseptic) and much greater leucocytosis (two hundred to three 
hundred per cent). 

Pilocarpine and antipyrin have been found by v. Jaksch and 
others to produce marked increase in the number of leucocytes 
when given subcutaneously. During the use of thyroid ex- 
tract Richter (Centralblatt f. inn. Med., 1896, p. 3) noted 
leucocytosis. 

A large number of observations on the effects of injections 
of bacteria or their toxins agree in the following results. 

1. Where the dose is very large the leucocytes are reduced, 
and the animal dies. 

2. Where the dose is not sufficient to kill the animal the 
temporary diminution in the leucocytes is soon followed by leu- 
cocytosis. 

3. Where the dose is slowly fatal the count of leucocytes 
oscillates up and down within wide limits. 

4. Animals previously rendered immune to the i^oison in- 
jected show little or no leucocytosis. 

5. Leucocytosis is more easily called forth and of greater ex- 
tent in young animals. 

6. Most pathogenic organisms act similarly, but bacilli and 
toxins of tuberculosis as a rule cause no leucocytosis. 

7. There is no evidence that any one variety of leucocyte is 
attracted by any particular bacillus or toxin. 

In the above sketch of therapeutic and experimental forms of 
leucocytosis no attempt has been made to give anything but 
the more interesting and important outlines of the immense 
amount of work done. 

Absence of Leucocytosis. 

It is of fully as great a practical assistance to us to know 
that in certain infective diseases leucocytosis is regularly ab- 
sent as to know those conditions in which it is to be expected. 
Among the most important diseases in which leucocytosis is 
conspicuously absent are : 

(a) Typhoid fever. 



LEUCOPENIA. 



97 



(6) Malaria. 

(c) Grippe (most cases). 

(d) Measles. 

(e) Eotheln. 

(/) Tuberculosis, including — 
Incipient phthisis. 
Miliary tuberculosis. 
Tubercular meningitis.^ 
" peritonitis. 
" ostitis and periostitis. 
" pleurisy. 
" pericarditis. 
In some of these affections, notably in miliary tubercle and 
the later weeks of typhoid, the leucocytes are diminished. 
Further details will be given under the special diseases. 

Leucopenia. 

Definition. — A diminution in the number of white cells in 
the peripheral circulation as compared with the number normal 
for the given individual. 

1. The effects of starvation and malnutrition in producing 
leucopenia have already been described. Such leucopenia is 
usually associated with lymphocytosis (see below). Cancer of 
the gullet is an example of this class. 

2. Short hot baths or prolonged cold baths produce tem- 
porarily the same result (Winternitz, loc. cit.). 

3. Most of the infective diseases in which there is no leuco- 
cytosis are sometimes characterized by leucopenia, e.g., grippe, 
measles, miliary tuberculosis, and other forms of pure tuber- 
cular infection, malaria, and especially typhoid, in the later 
weeks of which it is almost invariable, and is accompanied by 
lymphocytosis. 

Where a case of leuksemia is complicated by an infective 
disease (pneumonia, septicaemia) the number of leucocytes may 
fall below the normal. In a case recently occurring at the Mass- 
achusetts General Hospital in which a lymphatic leukaemia 
was terminated by septicaemia from glandular suppuration, the 

' Osier in the last edition of his text-book records that leucocytosis is 
often present in this disease. Most other observers have not found it. 



98 



CLINICAL BLOOD EXAMINATION. 



white cells fell gradually from 40,000 three weeks before death 
to 419 per cubic millimptre on the day of death. I have never 
heard of a lower count than this. The differential count was 
unchanged (lymphoc3^tes = ninety-eight per cent). 

4. In pernicious angemia the count is usually very low and 
may fall below 1,000 cells per cubic millimetre. Other forms of 
anaemia (rachitic, syphilitic) occasionally produce the same re- 
sult. 

Lymphocytosis. 

Lymphocytosis is a relative inau'ease in the lymphocytes or young 
cells in the hlood, with or without an increase of the total leucocyte 
count. The increase is relative to the percentage of young cells 
normal for the individual. When lymphocytosis and an in- 
crease of the total leucocyte count are present we cannot dis- 
tinguish the blood from that of lymphatic leukaemia, and the 
distinction must depend upon the course and symptoms of the 
case.' 

1. Such a condition (relative to the adult) occurs in healthy 
infant's blood and in many diseases of infancy, the blood seem- 
ing to have a tendency to return to the infantile type. Any- 
thing that retards the infant's normal gain in weight or general 
development retards its blood development as well. Thus a 
child of three, convalescent from a summer diarrhoea, may have 
fifty to sixty per cent of young leucocytes which would be normal 
for an infant of a few weeks, but for three years old is very high. 

2. Rickets and hereditary syphilis are perhaps the best known 
causes of relative lymphocytosis in children. Scurvy may pro- 
duce the same result. Dividing the ansemias of children into 
two groups, those that do and those that do not produce leu- 
cocytosis, it appears that the great majority of those whose 
total leucocyte count is normal show a relative lymphocytosis. 
This is the case irrespective of whether there is enlargement of 
the spleen or not. 

Sometimes the smaller, sometimes the larger lymphocytes 
are in the majority. Often no division between the two kinds 
is possible. 

* The lymphocytosis of chlorosis has been mistaken for lymphatic 
leukaemia (Schreiber) owing to too exclusive reliance on the results of the 
blood examination. The patient recovered. 



LYMPHOCYTOSIS. 



99 



3. In adults some forms of debility may be associated with 
relative lymphocytosis as above noted (page 82) . It is most 
marked, however, in chlorosis, peymicious ancemia, and the anae- 
mia secondary to syj^hilis, in the later weeks of tyx^hoid fever 
and in lactation. 

4. Certain cases of Graves' disease show marked lymphocy- 
tosis. How such cases differ from those that do not show it I 
have not been able to determine. 

5. It occurs also in luemoioliilia, goitr , in some cases of 
cervical adenitis, whether tubercular or lymphomatous, and iu 
tumors of the spleeyi. 

6. During the administration of thyroid extract a lymphocy- 
tosis has been recently noted by Perry (New York 3Iedical Bee- 
Record, August 29th, 1896). 

7. The larger forms of lymphocytes are increased in some 
splenic tumors (chronic " ague cake"), at the end of scarlet fever, 
in i^neumonia with delayed resolution (some cases), in measles, 
certain forms of phthisis and in the non-suppurative stages of 
small-pox ; also in many of the same diseases in which the small 
lymphocytes are increased. 

8. So far I have referred chiefly to relative lymphocytosis. 
Absolute lymphocytosis is very rare outside of lymphatic leu- 
kaemia. One case occurred at the Massachusetts General Hos- 
X^ital in 1894 — a child of six, who passed through an attack of 
bronchopneumonia with uneventful recovery, the onlj^ pecu- 
liarity of the case being the marked increase of white cells run- 
ning up to 94,600, sixty-nine per cent of ichicli ivere lymphocytes. 
During convalescence the blood became normal and the child 
left the hospital well in all respects. The case will be referred 
to later in the account of the blood of pneumonia. 

Diagnostic Value of Lymphocytosis. 

1. I have already suggested that the degree of health in 
persons not organically diseased might perhaps prove to vary 
directly with the percentage of adult cells in the blood. 

2. In children the same percentage is to a certain extent a 
measure of the child's degree of development — causes of leu- 
cocytosis being excluded, and the percentage normal for a child 
of the patient's age being taken as the standard. 



100 



CLINICAL BLOOD EXAMINATION. 



3. The diagnosis of obscure syphilitic disease may be sup- 
ported by the coincidence of lymphocytosis with eosinophilia. 

4. Absolute lymphocytosis in the presence of glandular 
tumors is our mainstay in the diagnosis of lymphatic leukaemia. 

Eosinophilia. 

Definition, — An increase in the percentage of eosinophils in 
the circulatory blood, with or without an increase in the total 
leucocyte count. 

The researches of Neusser, Zappert, Weiss, Klein, and others 
have brought the eosinophilic cells once more into the promi- 
nence which they lost when it became apparent that they were 
in no way peculiar to leukaemia. 

1. Leukaemia is occasionally^ associated with eosinophilia 
(see below, page 146), but in the majority of cases this is not so. 
As in normal blood, from one to three per cent of them are to 
be found. 

2. In infancy the percentage of eosinophiles is very often 
higher than in adults, so that in them eosinophilia may be con- 
sidered physiological. In adults its presence is often unex- 
plained. The eosinophiles are the most seemingly capricious 
of all blood cells. A certain amount of light has been thrown 
on them by the observations of Neusser and his pupils (Weiss, 
Schreiber, Klein, and others). 

3. Neusser noticed that eosinophilia occurs — 

(A) In many affections of the bones (sarcoma, leukaemia, 
osteomalacia). 

(B) In many affections of the skin (pemphigus, pellagra, and 
others). 

(C) In troubles involving the female genitals, especially the 
ovaries. 

(D) In disturbances of the sympathetic nervous system. 

That there is some relation between these seemingly uncon- 
nected sets of phenomena is shown by various other facts besides 
the presence of eosinophilia in them all. 

{a) Bone and genitals. 

Osteomalacia is most apt to occur in pregnancy and is cured 
in some cases by castration. 

(b) Genitals and sympathetic nervous system. 



EOSINOPHILIA. 



101 



The presence of all sorts of psychoses and vasomotor troubles 
associated with menstruation, pregnancy, and the climacteric, 
and the so-called " reflex" disturbances in connection with uter- 
ine or ovarian disease, are well known. 

(c) The connection of the skin with both of the last-men- 
tioned systems is seen in the trophic disorders and sympathetic 
dermatoses of hysteria and ovarian disease. 

Working out the suggestions of this theory Neusser and his 
pupils have found relative eosinophilia in the following affec- 
tions : 

1. Bones. 

Osteomalacia, malignant bone-tumors, pernicious anaemia 
(some cases), splenic-myelogenous leukaemia (occasionally). 
[The writer has seen slight eosinophilia in osteomyelitis.] 
Possibly the relative eosinophilia of normal infants' blood may 
be connected with the great activity of their bone growth. 

2. Diseases affecting the skin. 

Urticaria, x)ellagra, dermatitis herpetiformis, and pemphi- 
gus (constantly) ; some varieties of herpes, prurigo, eczema, 
lymphodermia perniciosa; the exanthems of scarlet fever and 
syphilis {not measles or small-pox), ichthyosis, lupus, myx- 
oedema. 

3. Genitals. 

Gonorrhoea, prostatitis, many ovarian tumors, before and 
during the early days of menstruation, puerperal mania, and 
the psychoses of menstruation, of the puerperium, and of the 
climacteric; in sexual neurasthenia, after coitus, and in lacta- 
tion. 

4. Sympathetic Nervous System. — The psychoses last men- 
tioned, hysteria, Basedow's disease, and some of those given 
under the next heading. 

5. Besides these general groups, Neusser has noticed another 
class of cases characterized by eosinophilia, namely, those in 
which some member of the group of xanthin bases is supposed 
to be in the system. In the so-called uric-acid diathesis the 
nuclein derivatives are transformed in the intestine into one of 
the xanthin bases, and their presence in the system appears to 
give rise to eosinophilia. 

At any rate we regularly find eosinophilia (according to 
JSTeusser) in diseases thought to be characterized by an excess of 



102 



CLINICAL BLOOD EXAMINATION. 



these substances in the system. Examples of this are found in 
gout, bronchial asthma, emphysema, certain forms of migraine 
and epilepsy, oxaluria, uraemia, tetanus, some gastro-intestinal 
troubles, ankylostomiasis, after injections of nuclein, pilocarpine, 
tuberculin, and in most non-malignant liver diseases. All these 
Neusser believes stimulate the sympathetic nervous system and 
hence the bone marrow, through the production of xanthin 
bases. In asthmatic patients he succeeded in producing a 
paroxysm by injecting nuclein subcutaneously. 

Possibly under this heading comes the eosinophilia after an- 
tipyrin, and that sometimes found in chlorosis, scurvy, chronic 
malaria, and phthisical patients with cavities. In the latter 
cases it has been suggested that the patients may inoculate 
themselves with tuberculin absorbed from their lung cavities. 

6. Tumors of the spleen are also accompanied by eosino- 
philia in some cases. Neusser does not explain this under the 
theory above sketched. 

Many acute mental troubles show eosinophilia, while chronic 
cases do not. 

Other causes of eosinophilia are phosphorus poisoning and 
injections of campherin. 

In Osier's clinic there has recently been observed and re- 
ported a case of trichinosis in which the eosinophilic cells were 
from the first increased, and continued to increase till at the 
time of death there was 64 per cent of eosinophiles in a leuco- 
cytosis of 25,000. 

We also find eosinophilia in many forms of syphilis and 
syphilitic disease of the spinal cord (tabes dorsalis). 

Diminution in Eosinophiles. 

1. During digestion. 

2. After castration. 

3. In febrile stages of pneumonia, grippe, typhoid, diph- 
theria, sepsis, and most iofectious diseases accompanied by leu- 
cocytosis. That this is not due simply to the presence of fever 
is shown by the fact that in malaria and scarlet fever, despite 
high fever, eosinophiles may be increased. 

In the post-critical stages of pneumonia and other infectious, 
diseases the eosinophiles swing up above the normal. 



MYELOCYTES. 



103 



4. Malignant disease, hemorrhage, and most of other causes 
of leucocytosis also diminish the eosinophiles. 

Diagnostic and Prognostic Value of Eosinophilia. 

Neusser has suggested the following points : 

1. In the diagnosis between puerperal mania and puerperal 
sepsis, eosinophilia points to the former. 

2. Between a tumor connected with the genital system and 
one not so connected, eosinophilia points to the former. 

3. In determining whether a given case of hysteria, neurosis, 
or psychosis is likely to be benefited by castration, the presence 
of eosinophilia favors the operation. 

4. In malignant disease an eosinophilia points to a metas- 
tasis in the osseous system (tumors of the spleen are not in- 
cluded in this rule) . 

5. In cases of doubtful syphilis eosinophilia combined with 
lymphocytosis (see above) speaks in favor of syphilis. 

6. The diagnosis of any obscure form of " uric-acid diathesis" 
is helped by finding an increase of eosinophiles. 

7. In distinguishing malignant liver disease from other liver 
disease eosinophilia points to the latter. 

1. In the prognosis of chlorosis, eosinophilia is favorable. 

2. In the prognosis of scarlet fever and scarlatinal nephritis 
the greater the eosinophilia the better the prognosis. 

3. After hemorrhage increased eosinophiles show active re- 
generation of blood and good prognosis. 

4. In pernicious anaemia eosinophilia is favorable for the 
same reason. 

MYELOCYTES. 

The occurrence of the myelocyte of Ehrlich in the circulat- 
ing blood is always to be looked upon as pathological, that is, 
as the intrusion of a variety of leucocyte naturally a stranger to 
the circulating blood and a permanent inhabitant of the marrow. 
Although it is so close morphologically to other varieties of 
leucocytes that we should certainly suppose it to be an inter- 
mediate stage between the large lymphocytes and the polymor- 
phonuclear neutrophiles, the fact that it does not occur outside 
the marrow in health spfeaks against the supposition. 



104 



CLINICAL BLOOD EXAMINATION. 



Of the occurrence of the myelocyte iu leukaemia and perni- 
cious anaemia mention will be made under those diseases. The 
object of this section is to give a list of the other conditions 
under which it ap]3ears. 

Neusser ' has found small percentages of myelocytes in urae- 
mia, carbonic-acid j)oisoning, diabetes, syphilis, puerperal 
mania, osteomalacia, Basedow's disease, and sarcoma, also dur- 
ing menstruation. 

Capps found considerable percentages near death in general 
paralysis (see Book II. , page 272) . 

J. J. Thomas found them in mj^xoedema. 

The majority of other references to them in literature relate 
to different forms of grave anaemia. For example : 

(1) Hayem"' speaks of cells apparently myelocytes (he did 
not use Ehrlich's methods) in cases of extreme anaemia. 

(2) E. Krebs^ found them in severe anaemia. 

(3) Loos' describes them in the anaemia of hereditary sj^phi- 
lis, and Kille' finds them in the anaemia of acquired syphilis, 

(4) Neusser' mentions their presence both in pernicious 
anaemia and in chlorosis. 

(5) Hammerschlag' made a similar observation. 

(6) Engel ^ noted their presence in a case of what he cau- 
tiously calls "pseudo-pernicious anaemia." 

(7) Arnold ^ mentions them. 

(8) Klein" gives a list of various diseases (besides leukaemia), 
in which they have been found, many of which are essentially 
anaemic conditions. 

(9) Holmes " has found them in phthisis. I can confirm 
this observation. 

^ Cited in Klein: Volkmann's "Samral. klin. Vortrage, " December, 
1893. 

2 "Du Sang," Paris, 1889, p. 382. 
=^Inaug. Dissert., Berlin, 1892. 

4 Wien. klin. Woch., 1892, p. 291. 

5 Loc. cit. , 1893, No. 9. 

s Loc. cit. , 1892, No. 42. 

^ Berlin klin. Woch., August 20th. 1894. 

^ Virchow's Archiv, vol. cxxxv. 

^ Loc. cit. , vol. cxl. 

'"Volkmann's "Sammlung klin. Vortrage," December, 1893. 
» New York Medical Record, September 5th, 1896. 



MYELOCYTES. 



105 



(10) The writer ' found tliem especially in the anaemia secon- 
dary to malignant disease (see page 305). 

Beside these conditions the writer has found them in 



Cases. 

Burns (large surface) , . 2 

Osteomyelitis, . 2 

Malaria, with anasmia, 1 

Cystitis and chronic starvation, 1 

Septicaemia, .3 

Bone tuberculosis, 1 

Rickets, 1 

Hodgkin's disease, . . 2 

Addison's disease, 1 



The most curious example of their occurrence known to me 
is the following : 

Mrs. W had been starving herself more or less for six 

months from motives of economy. Two weeks before I first 
saw her she began to suffer with cystitis. From both these 
troubles she made a rapid recovery, which has persisted now 
eighteen months. There was at the first count a leucocytosis of 
15,100; partly due to cj^anosis, as she had just been having a 
chill. The red cells were 7,300,000. Haemoglobin, eighty -seven 
per cent. Differential counts were as follows : 



Date. 

Number of cells counted. 


May 2d 
800. 
Per cent. 


May 6th 
1,000. 
Per cent. 


May 7th 
400. 
Per cent. 


May 8th 
400. 
Per cent. 


May 1.3th 

1,000. 
Per cent. 


"Polynuclear neutrophiles". . . 


82.7 


82.2 


83.6 


80.2 


68.5 




8.6 


12.5 


9.4 


11.3 


25.2 




8.2 


1.5 


2.0 


6.0 


5.2 


Myelocytes 


.5 


3.5 


4.0 


2.5 


.6 




.0 


.3 


1.0 


.0 


.5 



What caused the presence of myelocytes I do not know. At 
that time I had never seen them in any curable disease and was 
alarmed by their appearing, but this case proves that they are 
not always of any importance. 

In a general way their presence seems to have about the same 
significance as that of normoblasts. 

' Boston Medical and Surgical Journal, loc. cit. 



CHAPTEK IX, 



GENERAL PATHOLOGY OF THE BLOOD AS REGARDS HEMO- 
GLOBIN, FIBRIN, LIP^MIA, IVIELAN^MIA AND 
HEMORRHAGE. 

HEMOGLOBIN. 

As stated above, the lisemoglobin may increase and diminish 
in lines parallel to those of the red cells. In that case we sup- 
pose the amount of haemoglobin per corpuscle to be normal and 
the color index or valeur glohulaire is said to = 1. Where the 
haemoglobin is diminished more than the count of corpuscles, we 
say that the color index is less than 1. For example, if a man 
has 5,000,000 red cells per cubic millimetre and only 50 per cent 
of haemoglobin, we estimate the color index by simply reducing 
the count of cells to a stated percentage (5,000,000 cells — 100 
per cent of cells) and dividing this i^ercentage into the haemo- 
globin percentage — i.e., ^VV = 0-5 = the color index. There- 
fore 4,000,000 red cells (= 80 per cent) with 60 per cent of 
haemoglobin give a color index of = 0.75. 

The color index never goes above 1, except in pernicious 
anaemia (see below). As a rule when the red cells are above the 
normal the haemoglobin rises equally, sometimes it lags behind 
a little, but rarely if ever does it rise higher than the cells. 

In most anaemias, as has been pointed out, the haemoglobin 
suffers markedly before any considerable loss of red cells takes 
place. In other words, the corpuscles get thin before they die, 
and except in malaria, hemorrhage, etc., and in a few other 
cases they are not destroyed while in the full vigor of health. 

The loss of haemoglobin is loss of albumin, the chief constit- 
uent of the cells, and hence is usually loss of weight. 

In general the changes in the haemoglobin are best studied in 
connection with changes in the count of red cells, and so far as 
they have not already been mentioned will come in under the 
various special diseases. 



FIBRIN. 



107 



Fibrin. 

The fibrin network to be seen in normal blood during coagu- 
lation (see page 41) is increased in a considerable number of 
conditions. Hayem has studied these minutely, and described 
several varieties of arrangement of fibrin fibres as characteristic 
of special diseases, that is, he studied fibrin qualitatively as 
well as quantitatively, and also as regards the rapidity of its 
formation. 

The rate of fibrin formation is often not the same as the rate 
of coagulation. It is not parallel to the number of leucocytes or 
blood plates, at least not in all cases (malignant diseases, 
scurvy) . 

In a general way we expect increased fibrin in infectious and 
inflammatory diseases, but there are notable exceptions to this. 
The greater the exudation and the freer it is (in a cavity or 
on the surface) the thicker the fibrin network, while so-called 
interstitial inflammations or such conditions as parenchyma- 
tous nephritis show little increase in fibrin. The seat of the 
lesions has no considerable influence, except as it modifies the 
nature of the lesion. An abscess in one place has the same 
effect as an abscess elsewhere, provided it is equally free or 
equally confined, and of the same contents. 

Tuberculosis does not increase fibrin if uncomplicated. 
Leucocytosis and fibrin behave alike in many respects, espe- 
cially in relation to the vigor of resistance which the individual 
opposes to a given infection. When the individual is so weak- 
ened that he does not react well against the infection, the leu- 
cocytes and fibrin are but slightly increased, whereas in a vigor- 
ous individual the same infection would have markedly increased 
both fibrin and leucocytes. But neoplasms raise the count of 
leucocytes without changing the amount of fibrin. 

In a general way fibrin increases and decreases as fever does, 
but often persists after fever is gone. 

The most marked fibrin networks are seen in pneumonia, 
acute articular rheumatism, suppurative diseases, and in scurvy. 
In erysipelas it follows the leucocytes (increased in severe, 
not in mild cases). In the early days of grippe it is increased. 

The fever of hysteria or chlorosis shows no increase of fibrin 



108 



CLINICAL BLOOD EXAMINATION. 



and post-hemorrliagic anaemia with or without fever shows 
none. 

Fibrin is diminished in pernicious anaemia, not increased in 
leukaemia, typhoid, malaria, malignant disease, non-suppurative 
diseases of liver, nephritis (except interstitial nephritis, where 
it msij be increased), heart disease, purpura, hsemogiobinuria 
(sometimes decreased). 

The most valuable point about the fibrin appears to be the 
absence of any increase in malignant disease, whereby a diag- 
nosis between the affection and a suppuration may be helped. 
Otherwise the information given by it is chiefly confirmatory of 
impressions given by other features in blood examination. 

LlP^MIA. 

The blood invariably contains small quantities of fat, espe- 
cially during digestion (v. Jaksch 

In the blood of persons suffering from a variety of diseases 
such as phthisis, diabetes mellitus, obesity, alcoholism, ne- 
phritis, and in some dyspnoeic conditions, as well as in health, 
fat is occasionally to be seen in considerable quantities. Gra- 
witz'^ finds that if the blood is collected in a fine capillary 
tube and this is kept in a horizontal position for some time, fat 
rises to the surface like cream, and can be seen with an oil im- 
mersion lens in the form of fine drops. Gumprecht ^ demon- 
strated it with osmic acid, which stains the fat drops black, 
and proved them to be fat by dissolving them in ether, xylol, 
etc. 

Lipaemia has no special significance so far as is known, and 
is not characteristic of the diseases above mentioned. Its cause 
is unknown. 

[In almost any preparation of the fresh blood fat drops are 
to be seen unless the patient's skin is washed with alcohol be- 
fore puncturing. Even with these precautions a few drops 
may often be seen in healthy people's blood.] 

^ "Klin. Diagnostik," p. 75 (English translation). 

2 Loc. cit. , p. 160. 

3 Deut. med. Woch., 1894, No. 39. 



HEMORRHAGE. 



109 



Melan^mia. 

In malaria the occurrence of a black pigment in the leu- 
cocytes which have taken plasmodia into themselves, is gener- 
ally to be seen during and shortly after a paroxysm. Pigment 
free in the blood is only to be seen at the moment of seg- 
mentation among the new generation of parasites. The same 
condition has been observed in relapsing fever and in persons 
suffering from melanotic malignant tumors, the pigment being 
always in the white corpuscles. Presumably it must at some 
time be free in the plasma, but it is rarely if ever seen outside 
the cells. 

In Addison's disease Tschirkoff * observed pigment in the 
leucocytes. 

Hemokrhage. 

Women can stand a greater hemorrhage and yet live than 
men can. Children, on the other hand, succumb to compara- 
tively slight hemorrhages {cf. Blood in Infancy, page 335). In- 
dividual differences make a great difference in the ability to 
survive hemorrhage, and no exact amount of blood can be 
stated as the maximum that any one can lose and yet survive. 

Changes in the Blood Besulting from Hemorrhage. 

The red cells and haemoglobin of course suffer proportionally 
at first; later the haemoglobin in the newly formed cells is 
always deficient (see below). 

The striking point in the blood after hemorrhage is the evi- 
dence it gives us that even before the hemorrhage has ceased the 
other tissues begin to contribute fluid to make up the volume 
upon which life depends. The serum is markedly diluted by 
this fluid, but still serves to give the heart something to contract 
on and so prevents blood pressure from falling as fast as it 
otherwise would do. Were it not for such contributions from 
neighboring tissues the organism could sustain but slight 
hemorrhage without succumbing at once. We have then after 
hemorrhage a diluted or hydraemic blood, even though we do 

»Zeit. f. klin. Med., vol. xix., 1891. 

8 



110 



CLIXICAL. BLOOD EXAMINATION. 



not assist the efforts of nature by contributing fluid by intra- 
Tenons or rectal injection. Behier reports a case due to trauma 
in which the count was only 688,000 per cubic millimetre. 

Coagulation increases in rapidity the more blood is lost, so 
that after severe hemorrhage it takes place almost instantly. 

Blood EEaEXERAXiox. 

The regeneration of the blood after hemorrhage may be taken 
as typical of the same process in anaemia from other causes. 

Tlie length of time needed for full restoration to normal 
depends not merely on the (a) amount of blood lost, but also on 
the (b) age and nutrition of the patient as well as upon (c) the 
methods of treatment earned out and the existence of (d) other 
disease (typhoid, malignant disease, phthisis, etc.). 

Allowing for these other conditions we may say that, other 
things being favorable, the loss of 

I. Less than 1 per cent of the blood mass is made up in 2 to 5 days. 
II. From 1 to 3 " " " " " 5 " 14 

III. " 3 " 4 " " « « « 14 « 30 « 

The last amount means a very severe hemorrhage. Few 
surgical operations involve the loss of over three per cent, and 
after such accordingly we expect the blood to be normal again 
in two weeks, provided the individual is otherwise sound (see 
Malignant Disease, page 296). 

Young, well-nourished persons are of course quicker in mak- 
ing up losses than the old and weak. 

Blood Condition During Regeneration. 

1. Eed Cells. — (A) As previously mentioned, the hsemoglo- 
bin becomes relatively low as soon as the regenerative process 
is well established, and as recovery progresses the red cells are 
almost always normal in numbers for some time before the stat- 
ure, weight, and color of the individual cells is what it should 
be. A color index of 0.50-0.60 is not unusual — in short, what 
some call a " chlorotic" condition of the blood. 

(B) Qualitative changes are those already described on page 
72, namely: {a) Deformities in size and shape with an average 
diminution in size; (6) polychromatophilic cells; and (c) nucle- 



BLOOD REGENERATION. 



Ill 



ated corpuscles. These latter are almost exclusively of the nor- 
moblast type, but an occasional megaloblast has been observed. 

Blood Crises. — Yon Koorden was the first to notice that in 
some cases nucleated corpuscles are to be found in the circu- 
lation in great numbers for a few hours only, the blood examina- 
tion both before and after showing few or none at all. The 
name of " blood crisis" has been given to these sudden outpour- 
ings of nucleated red cells ; they are to be observed during re- 
covery from various forms of anaemia. 

2. Wliite Cells. — Immediately after a loss of blood we can 
usually find a decided leucocytosis despite the dilution of the 
blood (see above, Post-hemorrhagic Leucocytosis). 

This leucocytosis is in no way difierent from those occurring 
from other causes. The percentage of adult cells is increased 
as usual, and the eosinophiles often disappear. The leucocy- 
tosis is rarely very high, seldom reaching over 80,000. It is 
not invariably present, or if present sometimes is of very short 
duration. Thus in a patient whose red cells were reduced to 
3,200,000 by a profuse uterine hemorrhage the white cells 
counted next day were only 8,000; while in the next ward of the 
hospital was a man crushed in a railroad accident whose red 
cells were 1,280,000, and the white cells 28,000, the usual state 
of things. 

The leucocytes may be increased even by a cerebral Jiemor- 
rhage which is not large enough considerably to affect the red 
cells in most cases. Two apoplectic cases (with autopsy) ob- 
served at the Massachusetts Hospital showed : 

1. Ked cells 5,512,000, white cells 25,000, Hb. 85 per cent. 

2. Ked cells 5,560,000, white cells 15,600, Hb. 90 per cent. 
Whether the leucocytes are here affected by any influence 

other than that of hemorrhage I do not know. 

The effect of transfusion (intravenous saline solution) is ap- 
parently at first to increase the leucocytosis. 

D , a patient with traumatic rupture of the urethra, had 

had severe hemorrhage for forty-eight hours before it was 
checked at 1 P.M., November 1st, 1895. At 4 p.m., his pulse 
being 165, the couut showed: red cells, 3,304,000; white cells, 
10,400. He was at once given a pint of sterilized normal salt 
solution by intravenous injection under the strictest asepsis. 
Ten minutes after the transfusion the leucocytes numbered 



112 



CLINICAL BLOOD EXAMINATION. 



32,400. One hour later they were 24,700, and the red cells 
3,632,000. Four hours later leucocytes, 31,900; red cells, 
3,046,000. The later counts were as follows : 

Red cells; White cells. 

November 2d : good pulse 3,608,000 34,600 

2d (5 P.M.) : good pulse 2,944,000 30,200 

3d (4 p.m.) : good pulse 2,928,000 15,800 

13th..... 3,360,000 16,600 

A good recovery was made. 



Importance for Surgery op Blood Counting After 
Hemorrhage. 

Mikulicz, who as a surgeon should speak with authority and 
who always takes account of the condition of the blood in his 
cases, lays down (following Laker) the following rule: Never 
operate on any case ivJien the licemoglohin is heloio thirty per cent. 
The question of operating at once or waiting for recovery from 
"shock," is a very common one in the accident rooms of any 
hospital and is generally settled on general impressions of the 
patient's vigor. We know, say, that he has lost blood, but we 
have no way of ascertaining how much. If his " shock" is due 
to hemorrhage he may need transfusion ; if it is due to cerebral 
concussion or compression, the transfusion will do more harm 
than good. The blood count can settle these questions, and 
could reveal much which is now obscure, if it were more fre- 
quently employed in surgical cases and a standard like that of 
Mikulicz worked out. 

In cases of suspected ruptured tube in extra-uterine preg- 
nancy, the question of whether the patient is suffering from in- 
ternal concealed hemorrhage can be settled in manj^ cases by 
the blood count, which will show a decided loss of red cells if 
the hemorrhage is large, and thereby distinguish the condition 
from peritonitis, obstruction, or strangulated hernia, none of 
which affects the red cells. Any other concealed hemorrhage, as 
for instance from ruptured kidney or spleen or liver, may be 
indicated by the blood count when by other physical signs the 
diagnosis might be very difficult. 



CHRONIC HEMORRHAGE. 



113 



Summary. 

The blood count is of importance after cases of supposed 
hemorrhage. 

1. To ascertain whether such has taken place. 

2. Its extent. 

3. Whether operation is to be immediate or not. 

4. Whether transfusion is indicated. 

5. How soon the patient has got back enough blood to make 
operation worth while. 

Cheonic Hemorrhage. 

Piles, uterine disease, hsemophilia, purpura, and other causes 
may produce a long-standing drain on the blood. 

Some patients apparently can lose a little blood almost daily 
for years without acquiring any severe anaemia, and if the indi- 
vidual is otherwise sound and does not suffer from an underly- 
ing disease like phthisis, cancer, or nephritis, he can probably 
go on for a long time without showing any bad effects from the 
repeated small hemorrhages. How much he can stand we have 
no way of judging, for we cannot measure the amount of blood 
lost. When, however, such small repeated losses do produce an 
anaemia, regeneration is apt to be much slower than after a 
single large hemorrhage. The longer the drain has been going 
on the poorer the chance for recovery, and the slower the latter 
will be if it does take place. 

Gain in body weight does not always mean gain in corpuscle 
substance as well (see Malignant Disease, page 290) . 



BOOK II. 



SPECIAL PATHOLOGY OF THE BLOOD. 



PART I. 



DISEASES OF THE BLOOD. 



CHAPTER I. 
THE PRIMARY ANEMIAS. 
1. THE BLOOD IN PERNICIOUS ANEMIA 

The definition of the disease has been sufficiently explained 
before (see page 70) and we can proceed at once to the descrip- 
tion of the blood. 

1. Gross appearances. 

(a) The drop as it emerges from the puncture is often exces- 
sively pale and watery, but not more so than may occasionally 
be seen in secondary ansemia or chlorosis. Sometimes it is not 
nearly so pale as in other cases with equally low counts, a fact 
which may be due to the increased color index sometimes present 
(see below). In one case (color index 1.2) I have seen the 
blood as red as normal. 

Another appearance, which I have frequently observed in 
this and other anaemias, is an uneven, streaked color in the 
drop, as if the cells were unequally divided in the plasma. 

(b) As striking as the color of the drop is its great fluidity ; 
the rapidity with which it slips off the ear or finger often makes 
it difficult to suck it up in time. It is usually very slow in 
coagulating. 

2. The fresh specimen in most cases shows no rouleaux forma- 
tion, a diminution in blood plates and fibrin, and usually great 
variations in the size and shape of the corpuscles. Not infre- 
quently the deformed corpuscle shows active pseudo-amoeboid 
motions of its projecting points or of the cell as a whole. The 
great lack both of red and white cells is noticeable even in the 
slide and cover-glass specimen. 



118 



SPECIAL PATHOLOGY OF THE BLOOD. 



Red Cells and Hcemoglohin. 

(a) Quantitative changes (see Table I.). The average count of 
red cells in the fifty -two cases of my table is about 1,200,000, 
which may be taken as the average count in patients seen at the 
stage of the disease at which they feel sick enough to seek medi- 
cal advice. We very rarely get an opportunity to examine the 
blood in the early stages of the disease, so that we have to judge 
of them chiefly from the evidence given during the remission so 
commonly observed. In the relapse following such a remission 
the blood count may fall from 5,000,000 to 1,000,000 in a period 
of from six weeks to six months. In the later stages of the dis- 
ease 500,000 red cells per cubic millimetre is not rare, and if the 
diminution has been gradual, the patient may be up and about 
and able to do light work with a count no greater than this. T 
had an opportunity to observe such a case in the wards of Dr. 
r. C. Shattuck at the Massachusetts General Hospital five 
years ago, where for several weeks the blood count remained at 
or near 500,000, yet the patient was outdoors daily, read the 
papers, and seemed perfectly comfortable. 

The lowest count on record is that reported by Quincke — 
143,000 per cubic millimetre. 



TABLE I. 





Co) First Count. 


C6). Highest Count. 


(c) Lowest Count. 


Total 
















number of 


1 




Per cent 




Per cent 




Per cent 


exam- 


Red cells. 


hsemo- 


Red cells. 


haemo- 


Red cells. 


haemo- 


inations. 






globiUe 




globin. 




globin. 




1 


490,000 


? 


490,000 


? 


410,000 


9 


2 


2 


510,000 


20 


680,000 


V 


510,000 


20 


3 


3 


600,000 


24 
? 










1 


4 


630,000 


658,000 


* i ' 


45,000 




13 


5 


670,000 


9 


670,000 




670,000 




1 


6 


680,000 


20 


680,000 


'20 


680,000 


'26' 


1 


7 


735,000 


? 


1,500,000 


9 


730,000 


? 


3 


8 


784,000 


14 


784,000 


14 


784,000 


14 


1 


9 


842,000 


9 


842,000 


9 


842,000 


? 


1 


10 


896,000 


18 


896,000 


18 


430,000 


6 


3 


11 


896,000 


17 


3,800,000 


70 


608,000 


15 


20 


12 


962,000 


15 


1,028,080 


15 


962,000 


15 


3 


13 


988,000 


9 










1 


14 


992,593 


34 


1,080,000 


' '? ' 


992,593 


■34* 


2 


15 


1,096,400 


12 


1,096,400 


1*3 


624,000 


13 


4 


16 


1,060,524 


35 










1 


17 


1,111,000 


? 


1,111,000 


' '? 


756,000 


• Y* 


3 



THE BLOOD IN PERNICIOUS ANEMIA. 119 



TABLE 1. — {Continued). 





(a) First Count. 


(6) Highest Count. 


(c) Lowest Count. 


Total 
















number of 


■ 




Per cent 




Per cent 




Per cent 


^ exam- 




Red cells. 


hsemo- 


Red cells. 


hEenio- 


Red cells. 


liasmo- 


inations. 






globin. 




globin. 




globin. 




18 


1,113,000 


18 


2,820,000 


? 


1,038,000 


? 




19 


1,126,000 


? 


1,126,000 


? 


1,100,000 


9 


9 


20 


1,137,000 


20 


1,137,000 


2*0 


550,000 


15 


A 


21 


1,140,000 


20 


1,140,000 


20 


622,160 


25 


Q 


22 


1,150,000 


9 


2,802,000 




1,150,000 




ID 


23 


1,150,000 


80 










1 

X 


OA 


1,176,000 


29 










1 


25 


1,200,000 


15 










1 


26 


1,226,284 


25 


4,450,000 


"65" 


762,000 


? * 




27 


1,270,000 


16 


2,700,000 


30 






0 

IV 


AO 


1,288,000 


? 


1,910,000 


9 


1,288,000 






on 


1.289,000 


32 


1,628,000 


34 


1,121,000 


'34' 


5 


30 


1,300,000 


28 


1,300,000 


28 


970,000 


30 


2 


ox ' 


1,336,000 


28 


1,336,000 


28 


956,000 


20 


Q 

0 


oa 


1,344,000 


23 


1,344,000 


23 


758,000 


17 


Q 
0 


QO 

66 


1,493,000 


32 


1,500,000 


? 






2 


34 


1,498,000 


20-30 










\ 


S^i 
oo 


1,500,000 


35 


3,700,000 


'53' 


1,460,000 


'36' 


Q 


36 


1,582,000 


20 


4,760,000 


52 


1,624,000 


30 


X/0 


37 


1,583,000 


20 


1,768,000 


40 


1,500,000 


20 




38 


1,600,000 


25 


4,032,000 


80 


1,288,000 


23 


10 


3Q 


1,627,000 


? 






1 

1 


40 


1,755,000 


20 


1.755,000 


'26' 


1,117,000 


'26' 


2 


41 


1,768,000 


9 


2,458,000 


? 


1,768,000 


? 




42 


1,800,000 


28 


2,868,000 


41 


1,508,000 


31 


5 


43 


1,800,000 


25 








1 

L 


44 


1,800,000 


30 


1,800,000 


'36' 


1,768,000 


'22' 


3 


45 


1,819,000 


34 














1,872,000 


25 


1,872,000 


25 


1,144,000 


30 


3 


47 


1,884,000 




1,889,314 




1,330,000 




4 


48 


1,984,000 


'39' 


1,984,000 


"39' 


598,000 


'is* 


3 


49 


2,000,000 


20 


2,000,000 


20 


1,200,000 


20 


2 


50 


2,080,000 


35 


5.056,000 


70 


1,632,000 


50(?) 


9 


51 


2,076,000 


15 


4,500,000 


45 


1,384,000 


10 


10 


52 


2,524,000 


26 


2,524,000 


26 


1,280,000 


13 


5 




Average = 
















1,200,000 


26 










220 














Average = 4+ 



The great but temporary improvements above alluded to, fol- 
lowed by relapse, occur either with or without treatment. In 
the course of a few months the count of red cells may rise to 
normal, the nucleated corpuscles (see below) disappear, and the 
patient is apparently restored to health. I have followed one 
case through five such relapses in a period of three years be- 
fore the fatal issue came. Frequently the patient feels so well 



120 



SPECIAL PATHOLOGY OF THE BLOOD. 



during one of these remissions that he goes to work and is lost 
sight of, and, under such conditions, the incautious are apt to 
report "cure." 

The accompanying charts ^ show the three types usually met 



Chart I. 





























































0 










































































































50 


>3oaoo0o 






























































\ 














\ 
























5tf 
































































i 












































iOj 


ZOOOOOO 
























































































\ 










•> 








M 














































































































1000OOO 










































































































(o; 






V 







































































































- Red Cells 
Nafmotjlobin 



CWARTJI 



4500000 



a.000000 A0\ 



ioooooo ko: 





























































f 














































































t 










































































r- 
































\ 



































































































—Red Cells 
'•Hae/ho^lobio 



k5 00000 501 
kOOOOOO 404 
1500000 3Ql 
1000000 Ml 
500000 101 



CHAprnr 



























































is 
































































\ 













































































































































with; No. II. being, of course, only a fragment of No. I., while 
the steady progression of No. III. may have been preceded by 
a rise from a former downfall, though no such history was ob- 
tained. 

Looking over a considerable number of cases, one can 
hardly help being struck with the tendency of the count to 
remain near the figure 1,000,000. Cases rarely remain sta- 
tionary at, say, 2,000,000, and often die without sinking be- 
low 1,000,000. It seems as if some self-applying mechanism 

^ The number of perpendicular lines represents the number of weeks. 



THE BLOOD IN PERNICIOUS AN^.MIA. 121 

tended to arrest the destruction of corpuscles at or near this 
point (see Table I.). 

TABLE II. — White Cells— First Examination. 



No. 



White Cells. 



No. 



1 

2, 
3 
4 
6 
6 
7, 
8, 
9 

10, 
11, 
12 
13, 
14, 
15, 
16. 



400 
500 
800 
1,000 
1,000 
1,000 
1,500 
1,600 
1,800 
2,000 
2,000 
2,000 
2,000 
2,800 
2,800 
3,000 



17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27, 
28 
29 
30 
31 
32 



White Cells. 



3,200 
3,200 
3,500 
3,600 
3,704 
4,000 
4,000 
4,000 
4,000 
4, 200 
4,500 
4,720 
4,828 
4,900 
5,200 
5,300 



33 

34 

35 

36 

37 

38 

39 

40 

41 

42 

43 

44 

45 

46 

Average 



White Cells. 



5,600 

6,000 
6,000 
6,000 
6,400 
6, 500 
7,000 
7.200 
7,500 
7,600 
9,000 
9,600 
10, 000 
10,100 

= 4, 200+ 



In counting the red cells some difficulty and error may result 
from the very small size of some of the cells. It is especially 
important that the diluting solution should be clean and freshly 
made, else without the aid of a stain it may be hard to distin- 
guish the dwarf cells or microcytes from bits of extraneous sub- 
stance. 

Quantitative Changes. 

White corpuscles (see Table II.). — ^^The rule is a very consid- 
erable diminution in the number of leucocytes. Thus of forty- 
six cases which I have examined thirty were under 5,000, the 
average of all being 4,200+. 

[I have excluded from this series counts made immediately 
after hemorrhages and counts in infants. The latter are very 
apt to show a leucocytosis in connection with any form of 
anaemia.] 

As the disease progresses the leucocytes fall even more 
rapidly than the red cells and counts as low as 500 white cells 
per cubic millimetre are not uncommon. 

Leucocytosis when present in the blood of adult cases is al- 
ways due to some complication like hemorrhage or suppura- 
tion. 



122 



SPECIAL PATHOLOGY OF THE BLOOD. 



x4.s mentioued above, the blood plates and fibrin are mucli 
diminished. 

In four cases in which Dr. Lindstrom, of Boston, was kind 
enough to give massage, we were unable to see the slightest 
gain either in corpuscles or haemoglobin, such as can be pro- 
duced temporarily in most healthy persons. The observations 
of J. Mitchell on this point we were unable to confirm. 

Hcemoglobin. 

A certain number of cases of pernicious anaemia have a rela- 
tively high percentage of haemoglobin {e.g., 1,000,000 red cells 
and 35 per cent of hgemoglobin, or a color index of 1.75). In 
many cases this is not so, and in others we cannot tell 
whether it is so or not, owing to the unreliability of the v. 
rieischl instrument when used for very low haemoglobin per- 
centages. 

Of the 34 cases in the series on page 118, in which the haemo- 
globin was tested, a color index of over 1 was apparently present 
in 13, or 38 per cent, and a color index of less than 1 in 21 or 62 
per cent, of the cases. How many of these haemoglobin esti- 
mations may have been wrong I cannot say. 

From the frequency' with which we find the corpuscles larger 
than normal in pernicious anaemia (see below), we should 
expect that the haemoglobin icould be relatively high, and in 
a larger percentage of cases than the v. Fleischl instrument 
indicated. 

An increased color index is probably a bad prognostic sign. 
In the remissions of the disease when the cells are increasing 
fast, the haemoglobin lags behind and the color index is low. 
As the relapse follows, the color index in many cases progres- 
sively increases. Cases icJiose color index is low and in which 
the average diameter of the red cells is normal are apt to he 
gaining at that time, while those with high color index are apt to 
be losing at that time. 

The average color index in the 39 cases in which the haemo- 
globin and red cells were both tested was 1.04, the average 
pei'centage of haemoglobin being 26 and of corpuscles 24 
(= 1,200,000). 



THE BLOOD IN PERNICIOUS ANJEMIA. 



123 



Qualitative Changes. 

1. Bed Coj'jnisdes. 

(a) Increase in the average diameter of tlie cells is a very 
constant and striking feature of the stained specimens in this 
disease. In no other disease do so large cells or so many of 
them occur. 

Out of twenty-eight cases in which I have looked for this 
point, twenty-one showed the increase, as far as could be judged 
without actually measuring any large number of ceils. This 
does not mean that every cell is larger than normal, but that 
those larger than normal outnumber those undersized; the 
"macrocytes" are more numerous than the " microcytes." Oc- 
casionally we see cells over 20 ij- in diameter, some with nuclei, 
some without. 

(6) Deformities in Shape. — The eye soon gets used to the 
shapes assumed by the necrobiotic corpuscles and learns to dis- 
tinguish them from the distortions due to technique or to crena- 
tion. Most of them fall under one or another of the types sho^Ti 
in Plate lY. Litten has laid particular stress on the horseshoe 
forms, and thinks them peculiar to pernicious ansemia. The 
battledore and sausage-shaped forms are very common. In 
one case I found all the red cells of the latter shape, so that they 
looked at first sight like a lot of gigantic bacilli. That this ap- 
pearance was not due to the technique (as I had at first sup- 
posed) is probable from the fact that the rod-shaped cells did 
not point all in one direction as they would have done if pulled 
out of shape by the process of spreading. 

Occasionally we see cases with no considerable deformities 
whatever in the red cells. In nine cases out of thirty in which 
this point was observed, little or no deformity was noted. I 
cannot make out that such cases have any better or worse prog- 
nosis than others. I have never seen cases whose red cells were 
all undersized, but a normal average diameter was present in 
somewhat over one-quarter of the cases in which I have looked 
out for this point. 

^ Some writers advise the use of less heat than usual in dealing with 
cover-glass specimens of pernicious anaemia. I have not found this so 
and heat as usual for fifteen minutes at 100° C. 



124 



SPECIAL PATHOLOGY OF THE BLOOD, 



(c) Staining Properties of the Red Cells. — The white spots or 
streaks described by Maragliano, Hayem, and others are very 
often seen in the red cells of pernicious anaemia despite good 
technique. Some corpuscles are so pale in the centre that we 
see only the narrow ring of stained protoplasm at the periph- 
ery, a mere shell. Others are swollen up so as to show no sign 
of central biconcavity, and stain deeply and evenly all over. 

More common than in any other form of anaemia are the 
polychromatophilic red corpuscles (see Plate lY.) which with 
the Ehrlich-Biondi mixture stain brownish, purple, or gray, 
either as a whole or in parts. In the nucleated red cells the pro- 
toplasm is very apt to show this change, so that it is often diffi- 
cult to distinguish them from lymphocytes. In difficult cases 
we have sometimes to fall back upon the appearances of the 
edge or periphery, which in most red corpuscles shows some 
thin place or crinkle characteristic of a fiat cell, while the lym- 
phocyte gives us the more solid-looking outline of the spherical 
cell. 

All these microchemical changes can be better brought out 
with haematoxylon-eosin or eosin-metliyl-blue stains, but all 
that is needed for clinical purposes can be made out with the 
ordinary Ehrlich-Biondi mixture. 

Nucleated Red Corpuscles. 

Nothing further needs to be said in description of these forms 
(see above, pages 75-80). We have no exact method of estimating 
the number of nucleated cells either in relation to the whole num- 
ber of red cells or in a cubic millimetre. All we can do is to note 
the number seen in such an area of a cover-glass specimen as is 
covered while counting a given number of white cells, say 1,000. 
Knowing the ratio of red to white corpuscles, we can calculate 
from this number of nucleated red cells their approximate re- 
lation to the whole number of red cells. 

Thus if the ratio of white to red be 1:1000 (1,000,000 red 
and 1,000 white) and we have seen two nucleated red corpuscles 
while making a differential count of 1,000 white cells, the total 
number of red cells passed over must be approximately 1,000,- 
000 and the number of nucleated corpuscles about two in 1,000,- 
000 red cells or two in a cubic millimetre. Of course where 
leucocytosis is present and the ratio is raised — say to 1 : 150 



THE BLOOD IN PERNICIOUS ANAEMIA. 



125 



(10,000 white and 1,500,000 red) — finding two nucleated red 
cells while counting 1,000 white would mean that there were 
two nucleated cells in every 150,000 non-nucleated, or twenty 
in a cubic millimetre (or in 1,500,000 non-nucleated cells). 

Such calculations are inaccurate because we are never sure 
that the red cells and white cells are distributed in the dried speci- 
men exactly as they are in the blood. Part of the leucocytes 
may be accumulated at the edges of the cover-glass so that the 
ratio in the middle may be different from that in the circulating 
blood. 

Nevertheless we can get some idea of how plentiful the nu- 
cleated corpuscles are, and as their significance in prognosis 
depends far more on their kind than on their number^ greater 
accuracy as to the latter is not at present important. For in- 
stances, two megaloblasts per cubic millimetre mean a worse 
prognosis than twenty normoblasts, provided there are no other 
kinds present in either case. It is the ratio of megaloblasts to 
normoblasts and not the absolute number of each, that is of im- 
portance. 

In all of the thirty -eight cases of pernicious anaemia in which 
I have examined the blood, the number of megaloblasts has ex- 
ceeded the number of normoblasts, and as the cases grew worse 
the megaloblasts grew relatively more numerous (often abso- 
lutely as well). 

The range of variation in the number of nucleated cells pres- 
ent has extended in my series from six per cubic millimetre to 
7,100 per cubic millimetre (see Table III.). The calculation can 
be made by using the following formula. 

the number of white cells counted (by differential count). 
" " nucleated red cells seen while counting these. 

" " white cells per cubic millimetre (Thoma-Zeiss). 

X = number of nucleated red cells per cubic millimetre. 

The search for nucleated corpuscles in pernicious anaemia 
is sometimes the most laborious undertaking in all blood ex- 
amination, but it is also one of the most important. We may 
search two or three hours before finding one nucleated cor- 
puscle, but on that corpuscle may hang the character of our 
prognosis. If it be a megaloblast and no other nucleated 
red corpuscles are seen, the prognosis is bad, and it is impor- 
9 



Let n = 
" m = 
" p = 

p X — = 

n 



126 



SPECIAL PATHOLOGY OF THE BLOOD. 



ta,nt that we should know it. This is particularly true wheu 
the case is seen during a remission, for under these conditions 
we might never suspect a case of pernicious angemia but for the 
presence of megaloblasts. They are not always difficult to find; 
indeed, in one of my cases they were nearly as numerous as the 
white cells, but, as a rule, we do not get off with less than two 
hours' work. 

The following table (Table III.) shows the number of nucle- 
ated corpuscles per cubic millimetre in thirty of the cases ex- 
amined by the writer. 



TABLE III.— Number of Nucleated Red Cells per Cubic Millimetre 
IN Thirty Cases of Pernicious Anemia. 



Case Number. 


Total nucleated 
red cells. 


Megaloblasts. 


Normoblasts. 


Microblasts. 




1 


7,100 


5, 800 


1,325 


475 


2 


6,468 


3,476 


924 


2,068 


3 


854 


574 


266 


14 


4 


277 


277 


0 


0 




240 


160 


80 




6 


229 


123 


106 




7 


208 


130 


78 




8 


200 


134 


66 




9 


117 


103 


14 




10 


116 


80 


36 




11 


114 


95 


19 




12 , 


112 


96 


16 




18 


96 


96 


0 




14 


96 


84 


12 




15 


92 


59 


38 




16 


46 


26 


20 




17 


45 


36 


9 




18 


89 


33 


6 




19 


35 


32 


3 




20 


28 


20 


2 




21 


28 


21 


7 




22 


28 


28 


0 




28 


18 


12 


6 




24 


14 


14 


0 




25 


11 


11 


0 




26 


11 


10 


1 




27 


11 


9 


2 




28 


9 


6 


3 




29 


8 


7 


1 




:30 


3 


2 


1 





White Corpuscles. 

Qualitative Changes, — Unless the cover-glasses are spread 
unusually thick, it may take a long time to find enough leu- 



THE BLOOD IN PERNICIOUS ANEMIA. 



12? 



oocytes for an accurate differential count, so great is the leuco- 
penia in many cases. It is wortii while, therefore, to spread 
some cover-glasses more thickly than would be advisable if we 
had only the red cells to examine. Such preparations should 
be dried at once by artificial heat. 

Lymphocytosis is the chief fe&,ture (see Table IV.). 

Table IV.— Percentages of Leucocytes in Pernicious Anemia. 



Lymphocytes. 



No. 



1 
2 
3 
4 
5 
6 
7 
8 
9 

10 
11 
12 
18 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 



Per cent. 



79. 

71. 

61.6 

57.6 

57.2 

53.8 

51.5 

49.5 

47.9 

47.9 

45.9 

44.7 

43.7 

42.2 

41. 

40.8 

40.5 

38. 

38. 

37.8 

35.7 

35.6 

35.6 

34. 

33.1 

33. 

29.4 

27.2 

26.5 

24.2 

22. 

21.2 

19.8 

16. 



EOSINOPHILES. 



No. 



1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 



Per cent. 



9. 

6.2 

4.7 

4.6 

4.5 

4.4 

4.3 

4. 

4. 

3.7 

3.5 

3.4 

3.1 

2.8 

2.7 

2.6 

2. 

1.5 

1.5 

1.5 

1.5 

1.4 

1.2 

1.2 



Number of 
count. 



In 34 cases examined by myself the lymphocytes (large and 
small) averaged 45.9 per cent. About nine-tenths of these were 
small forms. As the fatal termination approaches, the percen- 
tage of lymphocytes rises. An extreme case of this change has 



128 



SPECIAL PATHOLOGY OF THE BLOOD. 



already been recorded on page 90. Two otlier cases showed re- 
spectively 71 and 79 per cent of lymphocytes a few days before 
death. The adult cells suffer proportionately. 

EosinopMles are occasionally increased, 9 per cent being 
present in one of my cases, 6.6 per cent in another. The aver- 
age of 49 examinations in my 34 cases is 2.7 per cent. 

Small percentages of myelocytes are the rule. They are 
present in 29 of my 35 cases. The following table shows the 
percentages : 



TABLE Y. 



No. 


Percentage | 
of myelocytes. 


Xo. 


Percentage 
of myelocj' tes. 


No. 


Percentage 
of myelocytes. 


1 


9.2 
8.8 
8. 
6. 

4.6 

4. 

3.6 

3.4 

2.7 

2.5 

2.2 

2.2 


13 


2.0 
1.8 
1.5 
1.2 
1. 
1. 
1. 
1. 
.8 
.8 
.6 
.6 


25 


0.6 
.6 
.5 
.4 
.3 
.2 
.0 
.0 
.0 
.0 
.0 

:2 per cent. 


2 


14 


26 


3 


15 


27 


4 


16 


28 


5 


17 


29 


6 


18 


30 


7 


19 


31 


8 


20 


32 


9 


21 


33 


10 


22 


34 


11 


23 


35 


12 


24 


Average = 



As has been explained above (page 105), the myelocyte is found 
in a great variety of affections, although very sparingly in most, 
but, so far as my observations go, its presence is more constant 
and the percentages run higher in pernicious an?emia than in 
any other disease except leukaemia. I am speaking now of j^er- 
centages. With a leucopenia such as is usually present in per- 
nicious angemia, 2 per cent of myelocytes means absolutely a 
very small number per cubic millimetre. 

Taking 4,200 leucocytes per cubic millimetre as the average 
for pernicious anaemia (see above page 121) 2 per cent of mye- 
locytes amounts to only 84 per cubic millimetre. In leu- 
kaemia the absolute number of myelocytes is seldom under 50,- 
000 per cubic millimetre. 

The more important characteristics of the blood of pernicious 
anaemia are as follows : 

1. Red cells about 1,000,000 per cubic millimetre. 

2. White cells much diminished. 



THE BLOOD IN PERNICIOUS ANEMIA. 



129 



3. Haemoglobin variable, sometimes increased relatively ( = 
high-color index). 

4. Deformities in size and shape of red cells in many cases. 

5. Increase hi average diameter of red cells. 

6. Polychromatophilic red cells. 

7. Megaloblasts more numerous than normobalsts. 

8. Lymphocytosis. 

9. Small percentage of myelocytes. 

The items italicized are the most important and character- 
istic. 

Diagnostic Value. 

1 . Pernicious ancemia and chlorosis may be indistinguishable 
without the examination of the blood. The pallor of the two 
diseases is not always different either in degree or in kind, and 
the symptoms and physical signs may be identical. 

The differential diagnosis is easily made by the blood. 
The red cells rarely reach as low as 2,000,000 in chlorosis and 
the number and degree of degenerative changes are less than in 
pernicious ausemia. Megaloblasts have been seen in chlorosis 
(Hammerschlag) but have never constituted a majority of the 
nucleated red cells present. In the great majority of cases the 
pallor and other signs and symptoms of chlorosis are due to 
lack of haemoglobin per corpuscle (for the corpuscles are not 
only pale but very small-sized), and not to a lack of corpuscles. 
The high-color index and large size of the scanty cells in per- 
nicious anaemia constrast strongly with this. 

The white cells are about the same in both diseases, though 
usually fewer in pernicious anaemia. Lymphocytosis is common 
to both diseases. Myelocytes are occasionally found in chlor- 
osis, but much less commonly than in pernicious anaemia. 

2. Pernicious Ancemia and the Ancemia of Malignant Disease. 
— Not long ago I examined the blood of a gentleman who had 
gradually and without assignable cause acquired a " lemon-yel- 
low" pallor, without loss of flesh, vomiting, pain, or any localiz- 
ing sign or symptom. The diagnosis of pernicious anaemia had 
been made. To my great surprise I found over 4,000,000 red 
cells, with only thirty-eight per cent of haemoglobin, and 18,780 
white cells, eighty-six per cent of which were of the adult type. 
One normoblast was seen. Fibrin was not increased. The 



130 



SPECIAL PATHOLOGY OF THE BLOOD. 



anaemia was evidently secondary, and the autopsy ten months 
later showed cancer of the stomach. 

Malignant disease may bring down the count of red cells to 
1,000,000 or lower, but in such cases leucocytosis is always 
present. As will be seen in the chapter on malignant disease, 
leucocytosis is by no means invariable in the ansemia of cancer- 
ous growth, but in those cases which cause such an anaemia as to 
resemble the counts of pernicious anaemia, leucocytosis is in- 
variable. This in itself is sufficient to exclude uncomplicated 
pernicious anaemia. Where an actual increase in the whole 
number of leucocytes is not present in malignant disease, there 
is often an increased percentage of adult cells, contrasting 
strongly with the increased percentage of young cells in per- 
nicious anaemia. Normoblasts and not megaloblasts are the 
rule in malignant disease. If megaloblasts are present they are 
in the minority, while in pernicious anaemia they are in the 
majority. 

3. Pernicious Ancemia and other Secondary Ancemias. — Almost 
all secondary anaemias which are severe enough to reduce the 
count of red cells below 2,000,000 follow the type of malignant 
disease and show leucocytosis. The great pallor and dyspnoea 
seen in connection with some cases of tuberculosis and nephritis 
rarely mean a low count of red cells, but simply a loss of 
haemoglobin. I remember two cases in adjacent beds at the 
Massachusetts General Hospital, both with extreme yellow pal- 
lor without emaciation; one had 1,020,000 and the other 4,100,- 
000 red cells, the haemoglobin in each being about thirty per 
cent. The first was pernicious anaemia, the second nephritis. 

Purpura, typhoid, lead poisoning, chronic malaria, and other 
diseases may reduce the red cells to a point as low as that seen 
in early stages of pernicious anaemia and may not he accompa- 
nied by leucocytosis; but the absence of changes most charac- 
teristic of the latter disease (a majority of megaloblasts, in- 
creased diameter and color index in the red cells) serves to make 
the diagnosis clear. ' 

4. Pernicious Ancemia and Leuhcemia. — Occasionally in in- 

' Another point of difference emphasized by Grawitz is that the plasma 
of pernicious anaemia has a relatively larger amount of solids than that of 
anaemia secondary to the above diseases. This is hardly a clinically ap- 
plicable test, but is said to be a valuable one. 



THE BLOOD IN PERNICIOUS AN^.MIA. 



131 



fants these two diseases seem to approach very near each other 
and are difficult to distinguish. In infancy, as is well known, 
any anaemia (primary or secondary) is apt to be accompanied by 
leucocytosis and an enlarged spleen. Further leukaemia, which 
in adults usually causes a relatively slight anaemia, affects the 
red cells much more strongly in infancy, and may reduce them 
to a number decidedly suggestive of pernicious anaemia. There- 
fore in both diseases we may have enlarged spleen, great anae- 
mia, and leucocytosis. 

The one characteristic i:)oint of leukaemic blood — the abun- 
dance of myelocytes — usually enables us to distinguish the two 
diseases, for although present in both diseases the myelocyte 
is much more plentiful in leukaemia. Unfortunately we have 
no way of fixing just hoio numerous myelocytes must be in 
order to constitute leukaemia. It is only in infancy and very 
rarely then that this difficulty arises, but at that period I am 
inclined to believe that we sometimes see conditions intermedi- 
ate between the two diseases, indicating the ultimate identity of 
the two. Their numerous clinical resemblances cannot here be 
discussed. (For further comment on this point see page 345.) 

Peognostic Yalue of the Blood in Pernicious Anemia. 

The prognosis is always very bad, but the following scheme 
indicates the presence of a severe or of a mild type : 



1. Severe (rapidly fatal), 
(a) Extreme progressive an- 
aemia. 
(h) High-color index. 
(d) Increase in size of red cells. 

(d) Degenerative changes. 

(e) Numerous megaloblasts. 
(/) Few or no normoblasts. 
(g) Lymphocytosis. 



2. Less Severe (shiver course), 

(a) Remissions . 

(b) Normal or low-color index. 

(c) Normal-sized cells. 

(d) No degenerative change. 

(e) Numerous normoblasts. 
(/) Few megaloblasts. 

(g) Normal percentage of adult 
cells. 



It has been thought by some observers that the absence or 
great scantiness of nucleated corpuscles indicated lack of any 
effort at regeneration on the part of the blood-making functions 
and hence a peculiarly malignant type of the disease. I have 
never seen cases in which no nucleated corpuscles were present. 



132 



SPECIAL PATHOLOGY OF THE BLOOD. 



but their scantiness lias seemed to me as a rule to be associated 
with a more sloiuly fatal type of the disease. 

No significance has seemed to me to attach to the presence 
of larger or smaller percentages of eosinophiles. 



Red cells 

White cells 

Haemoglobin . . 
Megaloblasts . . 

Normoblasts . . 

Size of red cells 

Lymphocytes.. 

Adult leuco- 
cytes. 
Myelocytes 



Pernicious 



About 1,000,000.... 
Usually decreased, 



Often relatively 
high. 

Constitute the ma- 
jority of the nu- 
cleated red cells. 

Less numerous 
than the megalo- 
blasts. 

Increased 

Increased 

Decreased 

Common 



Chlorosis. 



Rarely under 2, 

000,000. 
Usually normal. . . 



Always relatively 
low. 

Rare 



Occasional; always 
more numerous 
than meg a 1 o - 
blasts. 

Diminished 

Increased 

Decreased 

Rare 



Secondary 
anaemia. 



May be 1,000,000 

or less. 
Usually in- 

creased. 



Relatively low . . . 

Rare ; never more 
numerous than 
normoblasts. 

Common 



Various; not in- 
creased. 

Usually d i m i n - 
ished. 

Usually i n - 
creased. 

Rare 



Leukaemia in 
infancy. 



May be under 
2,000,000. 

Usually more in- 
creased than in 
any other dis- 
ease. 

Relatively low. 

Common. 



Common. 



Various; not in- 
creased. 
Usually increased. 

Usually d i m i n - 
ished. 

Usually more 
numerous than 
in other diseases. 



2. THE BLOOD IN CHLOROSIS. 

This has been already described for the most part under the 
heading of Secondary Anaemia. In many cases the two are in- 
distinguishable by the blood examination alone, the changes 
consisting simply in the presence of light, small-sized, pale, 
more or less deformed red cells whose number may or may not 
be decreased, according to the severity of the case. Leucocy- 
tosis is rarely if ever present in uncomplicated chlorosis, but is 
often absent in secondary anaemia. Normoblasts may be pres- 
ent in both. The chief points of distinction are : 

(a) The red cells are more apt to be uniformly undersized 
and under-colored in chlorosis, while in secondary anaemia we 
more often find normal cells among the diseased ones. 

(h) The color index may be lower in chlorosis than is com- 
mon in secondary anaemia, and this lowering is more constant in 
chlorosis. 

(c) Lymphocytosis, which is very common in chlorosis, is not 
so common in secondary anaemia. 



THE BLOOD IN CHLOROSIS. 



133 



(d) Nucleated corpuscles are less common in chlorosis than 
in anaemia secondary to malignant disease. 

(e) Coagulation is rapid, in contrast with the very slow clot- 
ting of pernicious anaemia and of many secondary anaemias. 
Yet fibrin is not increased. 

TJie Blood in Gross. 

The pallor of the drop is sometimes excessive, fully as great 
as in pernicious anaemia, and the liquid is very fluid and thin. 
Yet it coagulates very rapidly and our technique must be 
prompt. 

Eed Cells and Hemoglobin. 
Quantitative Changes. 

Hay em has recorded cases whose count was as low as 1,662,- 
000 and even 937,360 per cubic millimetre. Such figures are 
certainly rare in this country, and the striking fact is usually 
the slight numerical loss of red cells, considering the extreme 
pallor of the patients. 

The lowest count in the Massachusetts Hospital series was 
1,932,000, and in W. S. Thayer's sixty-three cases 1,953,000. 
The accompanying Table VI. , from the Massachusetts Hospital 
records, shows the range of red cells and haemoglobin in seventy- 
seven cases as counted when the patients first came under ob- 
servation. The highest counts (7,100,000 and 5,884,000) are 
undoubtedly due to some temporary stasis or concentration of 
the blood. 

The average of the 77 cases, 4,050,000 red cells per cubic 
millimetre, is remarkable in so nearly coinciding with Thayer's * 
series above referred to, the average of which is 4,096,544. 

The average haemoglobin percentage of this series, 41.2 per 
cent, is also very close to Thayer's (42.3 per cent). This gives 
us on the average a reduction of the corpuscle substance to one- 
half the normal, or to the equivalent of 2,250,000 healthy red 
cells ; 49 of the 77 cases have 4,000,000 or more red cells. These 
figures do not agree with those collected by v. Limbeck, in 
which only 99 out of 247 are over 4,000,000. But this prob- 

' See Osier's article on Chlorosis in the "American Text-Book of Medi- 
cine," vol. ii., 1894. 



134 



SPECIAL PATHOLOGY OF THE BLOOD. 



ably means simply that in this country the patients seek medical 
advice before their disease has advanced very far, while in Ger- 
many they wait longer before resorting to a hospital. For, as 
above explained, in all anaemias the individual corpuscles lose 
substance first and only after some time begin to decline in 
number. This is especially the case in chlorosis, although by 
no means peculiar to that disease. 

The color index is invariably low, as seen in the table, al- 
though it is rare to see it fall below .30. In only four cases of 
the present series did it go below that figure, the average being 
about .50. 

TABLE VI.— Chlorosis. 



No. 


Red cells. 


Per cent 
Hsemo^lo bin , 


Color index. 


1 


7 100 000 




. oo 


9 




uo 


. oo 


Q 


K «OA 000 


oo 


. OJ. 


A 


5 1^1 9 000 


•ll 


• rtU 


K 


4.88 000 




d.1 


a 


K AQO 000 


"^0 
ou 


.to 


ly 


A^R 000 


fiO 
ou 


. OO 


Q 


^ AAU. 000 
O, '±■±0, UUu 


oo 


. Oo 


Q 


K A^fi nno 


PiO 

ou 


AR 


1 0 


5 180 ROO 


35 


.34 


11 


5,176, 000 


37 




12 


5,136, 000 


50 


.49 


13 


5, 096,000 


58 


.56 


14 


5,080,000 


50 


.50 


15 


5,040,000 


78 


.78 


16 


5, 030, 000 


58 


.58 


17 


5, 000, 000 


35 


.35 


18 


4, 992, 000 


82 


.83 


19 


4,968,000 


40 


.40 


20 


4,960,000 


55 


.56 


21 


4, 910,000 


50 


.51 


22 


4,904,000 


65 


.61 


23 


4,904,000 


40 


.40 


24 


4,888,000 


38 


.38 


25 


4,712,000 


51 


.54 


26 


4, 712,000 


56 


.59 


27 


4,711,000 


42 


.42 


28 


4, 680,000 


48 


.52 


29 


4, 640, 000 


60 


.64 . 


30 


4, 600, 000 


50 


.54 


31 


4, 560, 000 


45 


.50 


32 


4,520,000 


32 


.35 


33 


4,448,000 


45 


.50 


34 


4,416,000 


40 


.45 




4, 380, 000 


54 


.62 


36 


4,312,000 


35 


.40 


37 


4, 250, 000 


67 


.80 



THE BLOOD IN CHLOROSIS. 
TABLE VI.— Chlorosis (Continued). 



135 



No. 



38 

39 

40 

41 

42 .* 

48 

44 

45 

46 

47 

48 

49 

50 

51 

52 

53 

54 

55 

56 

57 

58 

59 

60 

61 

62 

63 

64 

65 

66 

67 

68 

69 

70 

71 

72 

73 

74 

75 

76 

77 

Average 



Red cells. 



4,216,000 
4, 208,000 
4,170,000 
4, 160, 000 
4,128,000 
4,104,000 
4,096,000 
4,080,000 
4,072,000 
4,024,000 
4.016,000 
4,000,000 
3,986,000 
3, 985, 000 
3,944, 000 
3,920,000 
3,888,000 
3.800,000 
3,800,000 
3,688,000 
3,688,000 
3.680,000 
3,648,000 
3,648,000 
3,620,000 
3,512,000 
3,512,500 
3,504,000 
3,460,000 
3,320,000 
3,244,000 
3,200,000 
2,992,000 
2,992,000 
2,936,000 
2,584,000 
2,552,000 
2,472,000 
2,464,000 
1,932,000 



4,050,000+ 



Per cent. 
Haemoglobin. 



35 
32 
57 
25 

28 
30 
21 
52 
40 
44 
30 
61 
42 
30 
47 
37 
32 
40 
53 
48 
55 
37 
37 
20 
30 
26 
40 

34 

19 
34 
31 
26 
14 
19 
15 
18 
19 



41 



Color index. 



(!) 



(!) 



.41 
.38 
.70 
.30 

.34 
.36 
.26 
.63 
.50 
.55 
.37 
.76 
.52 
.36 
.60 
.50 
.42 
.52 
.70 
.64 
.73 
.50 
.50 
).27 
.42 
.37 
.56 

.50 

).29 
.56 
.51 
.44 

28 
38 
31 
37 
50 



50 



The striking contrast is with pernicious anaemia, rather than 
with secondary anaemia. In the former the color index, as 
above mentioned, averaged 1.04 in 39 cases. In secondary 
anaemia it is almost always below 1, but does not average so low 
as in chlorosis, although in individual cases it may be very low. 
For example, Osterspey quotes a case of gastric cancer with 



136 



SPECIAL PATHOLOGY OF THE BLOOD. 



a blood count of 4,230,000 red cells, and only 22 per cent of 
haemoglobin, a color index of .26. 

Eed Cells (Continued). 

Qualitative Changes. 

(a) The stained specimen shows a greater or less degree of 
pallor of the corpuscle centres corresponding so accurately to the 
diminution in haemoglobin that a jjractised observer can tell ap- 
proximately how low it is simply from the stained specimen. 
The pallor, however, is to be taken in connection with the size of 
the cells, for the diminution in hsemoglobin is not due simply to 
a bleaching out of the cells, but to their loss of size. Hence, 

{h) The diminution in the average diameter of the cells is a 
very important feature. Both in this respect and as regards the 
bleaching of individual cells, many cases contrast with most 
secondarj^ anaemias, in that a large proportion of the cells are 
affected alike, i.e, are small and pale, while in secondary anae- 
mia there are apt to be well-stained and good-sized or over- 
sized cells in every field. These last occur also in chlorosis, but 
less frequently as a rule. Hence the usually lower color index 
of chlorosis. In certain cases this distinction does not hold and 
the two conditions are identical in so far as the size and color of 
the red cells are concerned. It is to the white cells that we must 
look for help in differential diagnosis. 

(c) Deformities in size and shape are very common in all ad- 
vanced cases, but often absent in mild or moderate ones. They 
present no special peculiarities except that macrocytes are rela- 
tively rare and microcytes relatively common. In the severest 
cases, however, the macrocytes begin to get more numerous and 
we approach the picture of pernicious anaemia. 

(d) Degenerative changes (Maragliano) are not common but 
are occasionally present in severe cases. 

(e) Nucleated red corpuscles are very scanty even in advanced 
cases. Hay em never saw any, but most observers find them in 
small numbers after long search. They are almost always of 
the normoblast type, but megaloblasts have also been found. 

The scantiness of nucleated red cells is a point of contrast with 
the anaemia secondary to malignant disease, in which even in 
mildlj^ anaemic states we readily find nucleated corpuscles, while 



THE BLOOD IN CHLOROSIS. 



137 



in chlorosis, even in severe cases, a long search may show very 
few or even none at all. 

Specific Gravity. 

Chlorosis is usually agreed to be one of the diseases in which 
specific gravity and haemoglobin run parallel, and as the, inac- 
curacies and inconveniences of the v. Fleischl instrument are 
so great, it seems to the writer better to follow the specific 
gravity rather than the haemoglobin. The tables on page 31 
(Part I.) show how the inference from density to coloring matter 
can be made. A specific gravity of 1030 is not very rare. 



White Cells. 
A. Quantitative Changes. 

Leucocytosis is absent in uncomplicated cases. In the series 
in Table YII. the occasional leucocytosis may be due to digestive 
or to a variety of other influences (uterine troubles, etc.), which 
could not be excluded. 

TABLE VII.— Leucocytes in Chlorosis. 



No. 

1.... 

2.... 

3.... 

4.... 

5.... 

6.... 

7.... 

8.... 

9. ... 
10.... 
11.... 
12.... 
13.... 
14. ... 
15..., 
16.... 
17.... 
18.... 
19.... 
20.... 
21.... 
22. ... 
23.... 
24. ... 
25.... 
26.... 



White corpuscles. 



15,000 
14,400 
12,800 
12,000 
12,000 
12,000 
11,600 
11,200 
11,100 
10,800 
10,800 
10,500 
10,400 
10,000 
10,000 
10,000 
10,000 
10,000 
9,600 
9,600 
9,600 
8,500 
8,000 
8,000 
8,000 
8,000 



No. 



27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 



White corpuscle 



8,000 
7,949 
7,900 
7,600 
7,600 
7,600 
7,600 
7,600 
7,440 
7,200 
7,200 
7,200 
7,000 
7,000 
7,000 
7,000 
7,000 
7,000 
6,850 
6,800 
6,800 
6,600 
6,600 
6,400 
6,400 
6,200 



No. 



53 
54 
55 
56 
57 
58 
59 
60 
61 
62 
63 
64 
65 
66 
67 
68 
69 
70 
71 
72 
73 
74 
75 
76 



White corpuscles 



6,100 
6,000 
6,000 
6,000 
5,600 
5,600 
5,600 
5,200 
5,200 
5,200 
5,000 
4,800 
4,800 
4,172 
4,000 
4,000 
4,000 
4,000 
3,600 
3,600 
3,400 
3,200 
2,800 
1,500 



Average = 7,485 



138 SPECIAL PATHOLOGY OF THE BLOOD. 

The average in Thayer's sixty-three cases was 8,467; in the 
present series (see Table YII.) it is 7,485. 

As in pernicious anaemia, the worst cases are apt to have 
leucopenia, and as improvement progresses the white rise even 
faster than the red corpuscles. 

The absence of lencocytosis is the most important point in 
distinguishing chlorosis from secondary anaemia due to cancer, 
suppuration, etc. 

B. Qualitative Changes. 

LympJiocytosis is usually present, as in pernicious anaemia, 
wherever the disease is well marked, and sometimes even in 
mild cases. Thus Eieder found in 12 cases an average of 33 
per cent of young cells, the highest percentages being 53.7, 43.5, 
and 41.7. Either the small or the large lymphocytes may pre- 
dominate. In my own experience it has usually been the small 
forms. 

The adult cells suffer proportionally, their low percentage 
contrasting often with that of secondary anaemia associated 
with lencocytosis. Eosiuophiles are occasionally increased. In 
Eieder's 12 cases the average percentage was 3.5, the highest 
percentages being 9.6 and 7 per cent. 

Myelocytes are rare but have occasionally been observed in 
small numbers. 

Regeneration of the Blood. 

As the patients begin to mend under the influence of treat- 
ment, the blood changes are just the reverse of those seen during 
the development of the disease. First the corpuscles gain in 
numbers, the haemoglobin still remaining low; later and much 
more slowly the coloring matter, size, and weight of the cells are 
renewed. It seems as if the new-formed cells were of light 
weight and had to grow up, or be replaced gradually by cells of 
normal stature. The nucleated corpuscles and deformities dis- 
appear and the leucocytes shoot up often a little above the 
normal. 

Blood Plates. 



Usually considerably increased. 



THE BLOOD IN CHLOROSIS. 



139 



Summary. 

1. Blood as a whole : Yerj^ pale in marked cases, very fluid, 
but coagulates rapidly. Fibrin not increased. Specific gravity 
usually low, running parallel with the haemoglobin. 

2. Eed cells : Average 4,000,000 when patient is first seen, 
very rarely go below 1,000,000. The majority of them are 
small-sized, pale, often deformed. Nucleated corpuscles are rare 
(normoblasts as a rule). 

3. White cells, not increased. 
Lymphocytosis, occasionally eosinophilia. 

4. Blood plates increased. 

Diagnostic Value. 

1. The points of difference from pernicious anaemia have 
been discussed. 

2. It is important to distinguish it from simple debility, 
and from cases whose skin only is anaemic; in both of these 
conditions the blood is normal. 

3. From secondary anaemia it may be indistinguishable in 
case the latter be without leucocytosis. Where leucocytosis is 
constantly present and the percentage of adult leucocytes is in- 
creased, chlorosis (uncomplicated) can be excluded. Of course 
many of the complications which may occur in chlorosis are 
accompanied by leucocytosis. 



CHAPTEE II. 



LEUKEMIA AND HODGKIN'S DISEASE. 

The distinction between leukaemia and leucocytosis has been 
sufficiently dwelt on above. 

The vast majority of cases fall clearly under one or the other 
of two distinct types, the splenic-myelogenous on the one hand, 
and the lymphatic on the other. Pure splenic and pure myelog- 
enous cases are so rare that they may practically be disre- 
garded. The lymphatic forms usually show some enlargement 
of the spleen (as well as the marked glandular swellings), but 
nothing like the enormous hypertrophy of the splenic-myelog- 
enous type. On the other hand, the lymph glands may be 
slightly enlarged in cases of the splenic-myelogenous type, but 
much less than in the lymphatic form. 

Corresponding to these two clinical types we have two very 
different blood conditions. Mixed forms occur where some 
characteristics of each type are present, both clinically and in 
the blood examination, but these are rare. 

Either form may be acute or chronic, although the lymphatic 
form is much more apt to be acute and the splenic-myelogenous 
type to pursue a slower course. Thus of the five cases of lym- 
phatic leukaemia seen by the writer three were acute, one suba- 
cute (six months), and one chronic (over three years), while of 
twenty splenic-myelogenous cases all were chronic. 

1. Splenic-Myelogenous Fokm. 

The drop as it emerges from the puncture looks perfectly 
natural in color and is neither whitish nor chocolate colored. 
It flows very sluggishly, however, and is difficult to spread be- 
tween cover-glasses owing to the masses of white cells con- 
tained in it. Coagulation is slow. 



LEUK^^MIA. 



141 



Ked Cells. 

The diminution in red cells is moderate, averaging about 
3,120,000 in the thirty-four cases of Table VIII., A (here the 
five lymphatic cases are included). The patients are often not 
pale and may feel perfectly well. The haemoglobin is usually 
diminished, the color index apparently remaining about normal. 
It is difficult to read the v. Fleischl instrument in leukaemia as 
the presence of so many leucocytes gives a muddy tint to the 
liquid, not easy to compare with the red of the glass. 



Table VIII. — Leukaemia. 



Red cells, count. 



5,000,000 
4,877,000 
4,800,000 
4,288,000 
4,016,000 
3,760,000 
3,635,570 
3,605,000 
3,292,000 
3,200,000 
3,078,000 
3,010,000 
2,996,000 
2,938,000 
2,921,600 
2,868,000 
2,792,000 
2,738,000 
2,715,000 
2,576,000 
2,520,000 
2,322,222 
2,320,000 
2,256,000 
2,140,000 
2,112,000 
2,060,000 
2,016,000 
1,866,664 
1,420,000 
1,386,000 
1,358,000 
1,200,000 
408,000 



Average = 3,120,000+ 



No. 


White cells, count. 


1 


1,072,222 


2 


980,000 


q 




4 


800,000 


5 


756,000 


6 


748,000 


7 


656,000 


8 


626,600 


9 


570,000 


10 


500,000 


11 


492,000 


12 


454,000 


13 


430,000 


14 


428,000 


15 


400,000 


16 


394,000 


17 


386,000 


18 


340,000 


19 


320,000 


20 


290,000 


21 


260,000 


22 


220,500 


23 


213,000 


24 


188,000 




183,000 


26 


170,000 


27 


139,600 


28 


138,000 


29 


134,400 


30 


132,000 


31 


98,000 


Average = 438,000 



10 



142 



SPECIAL PATHOLOGY OF THE BLOOD. 



Qualitative Changes. 

The striking i:)oint is the presence of very numerous nucle- 
ated red cells even in the absence of any sign of anaemia. With 
over 4,000,000 well-formed and well-colored red cells, we may 
have hundreds of nucleated ones in every cover-glass. They 
are as numerous in this form of leuktemia as in the worst forms 
of pernicious anaemia, even though the patient may be feeling 
nearly well. 

Both normoblasts and megaloblasts may be seen, but in 
most cases the latter are much in the minority. Many of the 
normoblasts show fragmentation in their nuclei and occasionally 
true karyokinetic figures are to be seen. In the anaemic cases 
we find all the other changes in the red cells characteristic of 
anaemia, but the nucleated cells are always more prominent than 
in any other form of anaemia of a like severity. This shows 
that nucleated corpuscles are not to be thought of as evidence 
(like deformities in shape) of regenerative or degenerative 
<3onditions only. A special connection to the bone marrow is 
Tery clearly indicated, all the more so as in the lymx^hatic form 
of the disease in which the bone marrow is not afi'ected, nu- 
cleated corpuscles are much less numerous, appearing in small 
numbers even in the very anaemic cases and not at all in those 
^ho are not ansemic. 

Other qualitative changes are not marked and correspond 
to the degree of anaemia i^resent : often there are none at all. 

As the count of the white cells rises, that of the red may fall 
and vice versa : or the red cells may remain at a comparatively 
high figui'e despite the progress of the white. 

White Cells. 
Qv.a ntifa / ive Ch a nges. 

The average number per cubic millimetre in the thirty cases 
of Table Till., B I'the lymphatic cases being excluded) was 
438,000 at the time when the cases first came under observation. 
The highest count in this series is 1.072. ■222 and the lowest 
98,000. 

Cases are on record in which the white cells were actually 
more numerous than the red. The average ratio in my series is 



LEUKEMIA. 



143 



about one white to seven red. The highest ratio is 1 : 2, and the 
lowest 1 : 37. It is best to use the " red counter" with a dilution 
of 1 : 200 in counting the white cells, otherwise they are often too 
crowded for convenience. The hgematokrit is useful in this dis- 
ease and in any condition where the white cells are much in- 
creased, not to supersede the Thoma-Zeiss or to give us the ab- 
solute number of cells, but for comparative observations as to 
the length of the column of white cells from day to day in a 
given case. 

In the fresh specimen we notice that a large proportion of 
the white cells are not amoeboid, a point of marked contrast 
with leucocytosis, in which nearly all the leucocytes are amoe- 
boid. This is due to the fact that the myelocytes which form 
so large a portion of the leucocytes in this disease do not pos- 
sess the faculty of amoeboid motion. We should expect there- 
fore to find their nucleus free from the twists and distortions 
characteristic of the amoeboid (polymorphonuclear) cells. And 
this is in fact the case (see below). 

With or without the influence of therapeutic agencies the 
white cells may fall gradually to normal and remain there for 
some time, the patient feeling greatly improved. Such a case 
occurred under my observation, and the patient, a washerwoman, 
went back to work and afterward passed through an attack of 
lobar pneumonia in safety. 

At such a time, when no increase in the white cells is pres- 
ent, we should never suspect leukaemia, seeing the case for the 
first time, unless we chance to make a differential count; then 
the characteristic qualitative changes (see below) would be seen. 



Table IX. —Leukaemia (Splenic-Myelogenous) . 



Case. 


Percentage of 
myelocytes. 


Percentage of 
eosinophiles. 




1 


60. 


11. 


11 


2 


55. 


8. 


12 


3 


51. 


6.5 


13 


4 


50. 


6.1 


14 


5 


48. 


6. 


15 


6 


46. 


5. 


16 


7 


42. 


5. 


17 


8 


38. 


4. 


18 


9.. 


36. 


4. 




10 


33. 


4. 





Case. 



Percentage of 
myelocytes. 


Percentage of 
eosinophiles. 


32. 


3. 


31. 


3. 


30.3 


3. 


26. 


2.7 


26. 


2.5 


26. 


2.5 


21.4 


1.8 


20.4 


1.5 


'e = 37.7 


4.4 



144 



SPECIAL PATHOLOGY OF THE BLOOD. 



Qualitative Changes, 

The enormous number of myelocytes is the point of interest. 
The average percentage in my 18 cases was 37.7 per cent (see 
Table IX ), rising in one case as high as 60 per cent and never 
lower than 20 per cent. 

Taking the average total number of leucocytes as 438,000 
per cubic millimetre, the absolute number of myelocytes would 
be over 162,000 per cubic millimetre. So far as I am aware the 
highest count of myelocytes in any other disease is that men- 
tioned on page 128 in a case of pernicious anaemia, namely, 1,150 
per cubic millimeti'e. The contrast is sufficiently striking. I 
wish to insist upon this point, namely, that the blood of splenic- 
myelogenous leukaemia is absolutely peculiar and characteristic, 
and could not be confused with that of any other disease. Cer- 
tain writers of late years have concluded that because myelo- 
cytes do occur in a great variety of diseases as well as in leu- 
ktemia, therefore there is nothing peculiar about the blood of 
the latter affection. It would be as logical to say that because 
albumin and casts occur occasionally in the ui'ine of persons 
practically well, therefore there is nothing characteristic about 
the urine of acute nephritis. 

Between the largest number of myelocytes ever recorded in 
any disease other than leukfemia, and the smallest number ever 
found in the latter disease, there is as great a difference as there 
is between the minute traces of sugar to be found in normal 
urine and the marked glycosuria of diabetes mellitus. 

At the first glance the stained specimen of leukaemic blood 
seems to be composed mostly of myelocytes, but this is because 
they are on the average so much larger than the other forms of 
white cells, which, being packed away in the interstices between 
the large myelocytes, do not appear prominently at first 
sight. 

Although (as just mentioned) the average size of the mye- 
locytes is greater than that of any other kind of leucocyte, there^ 
is a great range of variation in their size, and some are hardly, if 
at all, larger than a red cell. (This is equally tme of the mye- 
locytes as seen in the bone marrow. See above, page 57.) 

The individual characteristics and variations in the myelo- 
cytes have been already sufficiently described on page 55. 



PLATE II. 

Fig. 1. — Both this and Fig. 2 are intended to be fac-similes of actual 
microscopic fields. 

(a) Note the cell between those labelled 8 and 9— apparently a polymor- 
phonuclear cell without neutrophilic granules. Such cells are often seen 
in this form of leukaemia. 

(5) Note also the cell at the extreme upper right-hand corner of Fig. 1, 
which it is almost impossible to classify either as a myelocyte or as a 
polymorphonuclear neutrophile, since it appears to be intermediate be- 
tween the two varieties. 

(c) Both the nucleated corpuscles are normoblast ; 9 has polychromato- 
philic protoplasm. The red cells show scarcely any deformities and very 
slight deficiency in coloring matter. 

Fig. 2. — (a) Note the deformities in size and shape of red corpuscles, 
owing to the anaemia present. 

(6) No lymphocytes are figured, as they made up only two per cent of 
the white cells in this case. Eosinophiles were absent. 

(c) Note that the contrast between this figure (leucocytosis) and the one 
above it (leukaemia) is not in the abundance of white cells but in the kind 
of white cell predominating among those present. 



Examination of tlie Blood. 



PLATE II. 



Figure I = Splenic-myelogenous Leucaemia 
Figure II = Leucoeytosis (cancer of kidney) 
Cells stained yellow = Red corpuscles 

1, 2. 3. 4 a. 5 = Polymorphonuclear neutrophiles 

6 = Lymphocyte 

7 a. 8, = Eosinophiles 

9 a. 10 = Nucleated red corpuscles 




Cells stained yellow = Red corpuscles 
All others = 
Polymorpho- 
nuclear- 
neutrophiles 



Scale of 



Figure II 
Leucoeytosis. 



^^^^ .^^^^ 




r 



WW 

ml^-'^ ^^^^ 




W0§ 



R. C. Cabot fee. 



Lith. Anst. t. E. A. Fanke, Leipzig, 



LEUKEMIA. 



145 



Polymorphonuclear Cells. 

Although absolutely the number of these cells is greatly in- 
creased, the number in each 1,000 leucocytes is considerably 
diminished. The average percentage in the eighteen cases of 
Table X. is 49.2 per cent, the figures ranging between twenty- 
six and sixty-six per cent. 



Table X.— Leukemia (Splenic-Myelogenous). 



No. 


Percentage of 
polymorpho- 
nuclear cells. 


Percentage of 
lymphocytes. 


No. 


Percentage of 
polymorpho- 
nuclear cells. 


Percentage of 
lymphocytes. 


1 


26. 

32. 

37. 

40. 

44. 

45. 

46. 

46. 

49.5 

50. 

50.6 


2. 

2. 

2.5 

2.5 

2.5 

2.6 

3. 

5. 

5. 

5. 

6. 


12 


51. 

54. 

55. 

61. 

62.3 

62.5 

66. 


6. 
8. 
8. 
9. 
9. 

18.9 
31. 

7.6 


2 


18 


3 


14 


4 


15 


5 


16 


6 


17 


7 


18 


8 




9 

10 


Average = 49. 2 


11 





The individual cells show a much greater range of variation 
in size, staining properties, and the size and shape of the nucleus 
than in any other condition. In most forms of leucocytosis, for 
example, one adult cell looks very much like another, but in this 
form of leukaemia we are often struck by — 

(a) Very small cells. 

(h) Dark stained or very pale stained cells, 
(c) Unusual shapes in the nuclei. 

Besides these variations we often see cells apparently be- 
longing to this tj^pe, but whose protoplasm shows no color what- 
ever. Such a cell is figured to the right of Plate II., Fig. 1. 
Other cells show a few granules scattered about against a per- 
fectly white background. The outer rim of the cell is usually 
stained faintly, so that we can hardly make out its outline. 

{d) There are always some cells on the border line between 
the polymorphonuclear and the myelocyte, and in regard to 
which decision must be arbitrary. We cannot help getting the 
impression that at any rate in this disease the two varieties are 
only different stages in the development of the same cell. 



146 



SPECIAL PATHOLOGY OF THE *BLOOD. 



Lymphocytes. 

It is here that the greater relative dimhmtion occurs, to make 
Toom for the incursion of the myelocytes. In percentages they 
are reduced from their normal, 20 to 30 per cent, to an average 
of 7.6 per cent, as in leucocytosis. But still their absolute num- 
I)er is always increased. Thus the lowest percentage present in 
Table X. (namely, two per cent) would mean 8,760 out of the 
average 438,000, the total leucocyte count per cubic millime- 
tre, and 8,760 is three or four times as many lymphocytes per 
cubic millimetre as are present in normal blood. 

The proportion of large and small forms among the lym- 
phocytes varies a great deal, but there is no such excess of the 
large forms as would be expected if the spleen were the source 
of these cells, as Ehrlich supposed. 

There is nothing peculiar about the lymphocytes which differ 
in no respect from those of normal blood. 

Eosinophiles. 

Like all the other varieties these are absolutely much in- 
creased. Relatively — hj percentages — they may or may not be 
so. In my series they ranged from 1.5 to 11 per cent, averag- 
ing 4.4 per cent, a slight increase over the normal. 

Many writers, wrongly interpreting Ehrlich 's observations 
on this point, have stated that an increased percentage of eosin- 
ophilic cells was the distinguishing mark of leukaemia, and 
even recent writers {e.g., Gilbert, Striimpell) continue to re- 
peat this false statement. 

The cell characteristic of splenic-myelogenous leukcemia is not 
the eosinophile hut the myelocyte. 

We distinguish several types of eosinophiles in leukaemic 
blood. 

(a) Ordinary (polymorphonuclear) eosinophiles. 
(h) Eosinophilic dwarf cells. 
ic) Eosinophilic myelocytes. 

(a) Needs no comment ; (]}) is simply a very small cell with 
eosinophilic granules; sometimes such cells are not over 5 
in diameter. They are not uncommon in this form of leukaemia 
and are very rare in any other disease. The same is true of 
{c), the eosinophilic myelocytes which are very rare in any 



LYMPHATIC LEUKEMIA. 



147 



other disease, except pernicious anaemia, where they are occa- 
sionally seen. 

These cells are like myelocytes except that their granules are 
eosinophilic instead of neutrophilic (see Plate I. and Plate II.). 
They are found in the marrow in considerable numbers and con- 
stitute the majority of the eosinophilic cells seen in this form of 
leukaemia. Other constituents of leuksemic blood are (occa- 
sionally) basophilic cells, white cells showing mitosis (especially 
the myelocytes) , and the so-called Charcot-Leyden crystals. (As 
these last have no diagnostic value and are not peculiar to any 
disease, no description of them will be given here. They ap- 
pear to be present wherever eosinophils are plentiful, e.g., 
in asthma, gonorrhoea, in the bone marrow, etc.). 

Neusser's perinuclear basophilic granules are said to be abun- 
dant in this disease, owing to the excess of uric acid in the sys- 
tem. 

During remissions, when the leucocyte count may fall to 
normal, the percentage of myelocytes remains large and the 
diagnosis could usually be made even if we saw the case then for 
the first time. This I have observed in two cases, and Thayer 
has had the same experience. 

LYMPHATIC LEUKEMIA. 

Although Fraenkel has maintained that all cases of lym- 
phatic leukgemia are acute and that therefore the difference be- 
tween the two forms of the disease rests simply on the rapidity 
of the process in the blood and clinically, there is no doubt that 
chronic lymphatic leukasmia exists. 

Fraenkel is enabled to maintain his position only by extend- 
ing the term acute to cover all cases whose symptoms last not 
more than four months. Six weeks is the limit agreed upon by 
most other observers. 

The writer has watched two cases of typical lymphatic leu- 
kaemia for periods of seven months and two years respectively. 
The latter was as little sick as anj^ case of leukaemia that I have 
ever seen and came over thirty miles from time to time to report 
at the Out-Patient department. His blood showed little varia- 
tion from the following figures: Ked cells, 2,300,886; white 
cells, 112,000. 



148 



SPECIAL PATHOLOGY OF THE BLOOD. 



The differential count always showed the overwhelming ma- 
jorit}^ (over ninety per cent) of small lymphocytes characteristic 
of the disease. The lymph glands were all much enlarged, the 
spleen just palpable. The patient kept about his work as a gar- 
dener for over two years. Grawitz has watched a similar case 
for over four years. 

Eed Cells. 

The count of red cells is often somewhat lower than in the 
splenic-m^^elogenous form of the disease, averaging 2,730,000 
in my cases. 

The point of interest is the comparative rainty of nucleated 
red cells, the abundance of which is so marked a feature of 
splenic-myelogenous leukaemia. They follow the grade of anae- 
mia present. Cases occurring in children show more abundant 
nucleated corpuscles (the same is true of all leukaemia in chil- 
dren) than those occurring in adults, and the megaloblasts, 
usually scanty, may equal the number of normoblasts. 

White Cells. 
Quantitative Changes. 

The numerical increase is not nearly so marked as in the 
splenic-myelogenous form. The average ratio of white to red 
cells is about 1 : 40 instead of 1:7, and we never see counts 
reach the height common in the other form of the disease. 
The highest count of my series was 220,000 and the lowest 
30,000, the average being 141,000 as compared with 438,000 in 
the other form. 

Qualitative Changes. 

Lymphocytes (small forms, large forms, or a mixture) i^ake 
up usually over ninety per cent of all the leucocytes present. 
In some cases they are all nearly of one size, while in others we 
find every gradation from the smallest to the largest, so that it 
is absolutely futile to attempt to separate them into "large" 
and " small. " Two of my cases were made up wholly of the 
small forms all under 11 in diameter, two were composed 
largely of forms over 15 !j- in diameter, while one showed every 
intermediate size. 



PLATE III. 

(a) Lymphatic Leukcemia with Excess of Small Lymphocytes. 

One polymorphonuclear cell is present. All the rest are lymphocytes 
and exemplify the variations in the morphology of the cell occuring in 
this and other diseases as well as in health, e.g., variations in the staining 
of the protoplasm and nucleus, indentation and even division of the 
nucleus. 

Note that the scale of the whole of Plate III. is larger than in the other 
plates (see scale of fj.). 

(b) Lymphatic Leukcemia with Excess of Large Lymphocytes. 

The symptoms, signs, and course of these two cases were closely simi- 
lar, both subacute (eight weeks). 

Note the lack of chromatin in both nuclei and protoplasm of large 
lymphocytes. The plasma around them or their extreme edge took most 
of the stain. The brown tint of the red cells is due to underheating. 



Examination of the Blood. 

PLATE III, 



a 




Lymphatic Leucaemia 

a. Small Lymphocytes in excess 

b. Large „ „ „ 



R. C. Cabot fee. 



Lith. Anst 



LYMPHATIC LEUKAEMIA. 14^ 



Table XI.— Lymphatic Leukemia. 



Case. 


Percentage of 
lymphocytes. 


Percentage of 
polymorpho- 
nuclear cells. 


Percentage of 
myelocytes. 


Percentage of 
eosinophiles. 


1 


98.6 


0.5 


0.8 


0.0 


2 


98.6 


1. 


.37 


.1 


3 


96.5 


3.4 


.0 


.1 


4 


94. 


5.7 


.37 


.0 


5 


91.8 


4.6 


2. 


1.6 


Avera 


ge = 95.9 


3.04 


0.7 


0.36 



Sometimes, especially where the large cells predominate, the 
staining is very faint throughout the nucleus and protoplasm 
(see Plate III. , 6) , so that at first sight we should think some- 
thing was wrong with our technique. Other forms of leuco- 
cytes in the same preparation, however, will stain normally, 
showing that the trouble is in the lymphocytes and not in the 
technique. 

The protoplasm may be entirely unstained as in most of the 
cells in Plate III., 6, or it may stain pale gray or pink. In 
other specimens, especially those of the small-cell type (Plate, 
III. , a) the lymphocytes stain well. Their nuclei are frequently 
indented or even divided in two (this occurs also in normal 
blood, but less often) . 

In acute cases Litten has noticed fatty degeneration in the 
leucocytes (11th Cong. f. inner. Med., 1893). 

The following figures illustrate the influence of a septicaemia 
(from suppurating cervical glands) which ended the life of No. 
3 in the above Table XI. 



Date. 



April 3d 

" 4th 

" 6th 

" 8th 

« 10th 

" 12th 

« 13th 

" 20th 

" 21st 

" 22d 

" 24th 

" 28th 

" 29th 

Death on the 29th 



Number 
of leucocytes. 



31,600 
31,000 
28,505 
44,000 
31,500 
40,000 
Sepsis began, 
5,661 
4,000 
3,400 
3,222 
800 
471 



Percentage of 
lymphocytes. 



96.5 
93.6 
95.5 

92. 
94.7 



150 SPECIAL PATHOLOGY OF THE BLOOD. 



Zeissl's case, also of the lymphatic form, showed the follow- 
ing: 



Date. 


White cells. 


Percentage of 
lymphocytes. 


Percentage of 
adult cells. 




80 000 


Qfi 


4 


" 24th 


11.Q 000 






26th 


119,000 






" 29th 


122 000 


97.8 


2. 


October 6th 


140,000 






9th 


Pneumonia began. 


99. 


1 


10th 


119,000 






11th 


98,000 






12th 


68.500 






13tli 


43,500 


88.7 


11.3 


14th 


50,000 






15th 


9,350 


85.4 


14.6 


16th (A.M.) 


133,200 






16th (P.M.) 


172.000 


75. 


25. 



Summari/. 

The leading characteristics of leuksemic blood are as follows. 

(a) Splenic-myelogenous Form. 

1. Ked cells about 3,000,000, nucleated forms very numerous. 

2. White cells about 450,000, of which 

3. Myelocytes form about thirty per cent. 

(b) Lijrapliatic Form. 

1. Eed cells about 3,000,000 or lower; nucleated forms rare. 

2. White cells about 100,000 or lower, of which 

3. Lymphocytes form over ninety per cent (the large or the 
small forms may predominate) . 

4. Myelocytes and eosinophiles very scanty. 

(c) Mixed forms occasionally occur, partaking of the charac- 
teristics of each of the above. 

Diagnostic Value. 

Leukaemia is distinguished by the blood examination from 

1. Hodgkin's disease: («) splenic, (h) glandular. 

2. Tumors of the spleen and vicinity {e.g., kidney or retro- 
peritoneal glands) . 

3. Enlargements of the lymphatic glands from tuberculosis, 
syphilis, malignant disease. 

4. Hydronephrosis. 

5. Huge leucocytosis from any cause. 



LYMPHATIC LEUKEMIA. 



151 



6. Chronic malaria. 

7. Amyloid disease. 

1. Leukcemia and Hodghiii's disease (lymphadenoma or 
pseudo-leukaemia). The pathology of the two diseases is iden- 
tical but for* the blood count. In Hodgkin's disease the blood 
is normal, or shows at most a moderate anaemia or leucocytosis 
(adult cells alone increased), and the diagnosis is easily made. 

2. Tumors of the spleen and more especially of the kidney are 
very apt to be mistaken for leukaemia. Within a single year I 
have been asked to examine the blood in three cases of " leu- 
kaemia," all of which turned out to be malignant disease of the 
kidney. In all of these there was a large tumor resembling the 
spleen in the left hypochondrium and a very large increase of 
white cells. In two of them the blood was examined fresh and 
the great number of white cells in the slide taken as evidence 
confirmatory of leukaemia. The stained specimen, however, 
showed only marked leucocytosis with ninety per cent of adult 
cells of the ordinary type and no myelocytes. Other large 
tumors of this reg-ion. showed similar results. 

3. Adenitis with hyperplasia due to tuberculosis shows 
usually normal blood ' and is thus easily distinguished from leu- 
kaemia. Leucocj^tosis is often present in syphilitic cases and 
still more marked in those due to cancer or sarcoma, but the 
counts rarely reach 30,000 and myelocytes are absent or very 
scanty. 

4. One case of hydronephrosis in which the distention of the 
sac was so great that it presented as a hard, solid tumor on the 
right hypochondrium, was taken for leukaemia by a competent 
observer some years ago. The normal blood examination re- 
vealed the mistake, and excluded also malignant disease in all 
probability. The diagnosis was only reached, however, at the 
autopsy. 

5. Huge leucocytosis in pneumonia or malignant disease 
may often cross the old boundary line of 100,000 white cells, 
beyond which none but leukaemic cases were supposed to ven- 
ture. The differential count sets us right instantly, showing 
ninety per cent or so of the increase to be made up of ordinary 
adult leucocytes. 

6 and 7. The large spleen and cachectic appearance associated 
' Sometimes marked leucopenia. 



152 



SPECIAL PATHOLOGY OF THE BLOOD. 



with chronic malaria and long-standing suppurations may be 
easily distinguished fi'om leukaemia by the absence of anything 
more than anaemia and leucocytosis in the blood. 





Red cells. 


White cells. 


Young 
leucocytes. 


Adult 
leucocytes. 


Myelo- 
cytes. 


Nucleated 
red cells. 


Leukaemia (splenic- 


About 


450,000 ± 


About 7.6 


About 50 


About 37 


Very 


myelogenous). 


3,000,000 


per cent. 


per cent. 


per cent. 


numerous. 


Leukaemia ( 1 y m - 


About 


100,000 ± 


About 96 


About 3 


Absent. 


Rare. 


phatic). 
Hodgkin's disease . . 


3,000,000 


per cent. 
Normal. 


per cent. 






About 


7,500 ± 


Normal. 


Absent. 


Absent. 


normal. 










Tumors of or near 


Usually 


20,000 to 


Greatly 


Greatly 


Few if 


Few. 


the spleen. 


diminished. 


40,000 ± 


decreased. 


increased, 


any. 




Leucocytosis in gen- 
eral. 




May be over 
100,000 


Greatly 
decreased. 


Greatly 
increased. 


Few if 


Few at 




any. 


times. 


Chronic malaria 


Much 


Somewhat 


Usually 


Usually 


Few if 


Few. 




diminished. 


increased. 


increased. 


decreased. 


any. 




Amyloid disease. . . . 


Usually 


Usually 


Usually 


Usually 


Absent. 


May be a 




diminished. 


increased. 


decreased. 


increased. 




few. 


Hydronephrosis — 


Normal. 


Normal. 


Normal or 


Normal. 


Absent. 


Absent. 






decreased. 









Effect of Intercukeent Infections. 

There are on record seventeen cases in which leukaemia (acute 
or chronic) has been complicated with some intercurrent infec- 
tion, with marked effect upon the blood in all but one. This 
single case was an acute rheumatic arthritis reported by Richter 
in the discussion of Fraenkel's article in the Deutsche medictni- 
sche Wochenschrift for 1895 (Nos. 39, 43, and 45), p. 639. Here 
the blood remained unchanged. 

Miiller's * case of lymphatic leukaemia was complicated by a 
septicaemia and the count of white cells rose from 180,000 to 
400,000 per cubic millimetre, with a marked increase in the per- 
centage of polymorphonuclear cells. Here was a genuine leu- 
cocytosis added to a leukaemia. 

With the exception of these two cases, all those hitherto 
published have shown a marked progressive decrease in the total 
number of leucocytes without any change in the percentages of 
the different varieties in twelve, while the other five showed like 
Miiller's an increased percentage of the polymorphonuclear cells 
despite the decrease in the total leucocyte count. 

Various infections — miliary tuberculosis, pneumonia, grippe, 
erysipelas, abscess of kidney, septic lymph glands — alike de- 

1 Miiller: Deut. Archiv fiir klin. Med., 1892, vol. 50, p. 47. 



LYMPHATIC LEUKAEMIA. 



153 



creased the leucocyte count. In one case a rise just before 
death was observed. ' 

Thus in Henck's case the leucocytes fell from 400,500 to 
89,000, in one of Muller's from 246,900 to 57,300, in Kovacs' 
from 67,000 to 17,000, in Zeissl's from 140,000 to 9,350. I 
have already mentioned a case of lymjjhatic leukeemia (page 149) 
in which the leucocytes fell from 40,000 to under 500, this last 
being on the day of death. In this case the percentages of the 
different varieties of leucocytes remained entirely unchanged. 

It appears, therefore, that when an infection complicates 
leukaemia we may have — 

1. No effect (see case of rheumatic fever as a complication, 
just mentioned). 

2. A genuine leucocytosis on top, so to speak, of the leu- 
kaemia, with an increased percentage of polymorphonuclear cells. 

3. A decrease in the leucocyte count with or without an in- 
crease of polymorphonuclear cells. This decrease is by far the 
most common result and ma,j go far below normal as death ap- 
proaches. 

Goldschneider ^ found that by the injection of splenic extract 
and other substances he could bring about a similar diminution 
in the number of leucocytes, but that, as in the case of intercur- 
rent infections, this diminution was not accompanied by any im- 
provement in the patient's condition and death followed as 
usual. 

^1. Eisenlohr : Virchow's Archiv, toI. 73, . . . . lease. 

2. Henck : Virchow's Archiv, vol. 78, 1 " 

3. Quincke: Ref. in Miinch. med. Woch., No. 1, 1890, . 1 " 

4. Stintzig : Ibidem, 1 " 

5. Ortner: Wien. klin. Woch., 1890, p. 832, . . . 1 " 

6. Miiller: Deut. Arcliiv f. klin, Med., 1891, vol. 48, and 

1892, vol. 50, .2 cases. 

7. Kovacs: Wien. klin. Woch., 1893, p. 701 . . .1 case. 

8. Fraenkel: Deut. med. Woch., 1895, p. 639, . . . 2 cases. 



11. Freudenstein : Ref. by Fraenkel, loc. cit., . . .1 case. 

12. Zeissl: Wien. klin. Woch., May 14th, 1896, . . . 1 " 



9. Heubner : Ibidem 
10. Richter : Ibidem 




1 case. 
3 cases. 



13. Personal observation 



1 



Total, . ... 
2 Discussion of Fraenkel' s article, loc. cit. 
11 



17 cases. 



154 



SPECIAL PATHOLOGY OF THE BLOOD. 



Abscesses occurring iu leiik^emic patients are filled with adult • 
leucocytes as ordinary abscesses are, and do not contain mye- 
locytes. 

HODGKIN'S DISEASE. 

(Fseiido-Leukcemia, Lymphoma). 

The diagnosis of this disease is impossible without the blood 
-count. Its pathology is identical with that of leukaemia and 
even post mortem the two diseases are indistinguishable so far 
as the lesions outside of the blood are concerned. Yet the 
blood is in no way peculiar, but presents in most cases all the 
characteristics of the normal tissue. Its value is as negative 
evidence, telling us in a given case that leukaemia is absent even 
though all the other signs and symptoms may be those of leu- 
caemia. 

(I.) Transitions from Hodgkin's disease to leukaemia have 
taken place under the eyes of competent observers, but they 
are very rare. Onl}^ three such cases are on record so far as 
I know, that of Fleischer and Penzoldt,' that of Hosier,'' and 
one reported by Senator, ^ where two sisters came under obser- 
vation, both suffering from Hodgkin's disease. One died of 
it ; in the other the blood changed to that of leukaemia before 
death. 

Doubtless many of the other cases supposed to exemplif^^ a 
similar transition were really cases in which a leucocytosis arose 
owing to some inflammatory complication, as not uncommonly 
occurs (see below. Table XII.). 

From the existence of these very rare cases of a transition to 
leukaemia it has been supposed, especially by French observers, 
that Hodgkin's disease is simply an early stage of true leu- 
kaemia and that this would always become apparent were it not 
that the patients die of some intercurrent disease before the 
;signs of leukaemia have time to show themselves in the blood. 
One difficulty with this view is that there occur chronic cases 
which last from eight to ten years without any change in the 
Hood. Another difficult}' is that the transition is in fact rare 

1 Deut. Arch. f. klin. Med., yol. 17. 

- Ziemssen's "Handbuch d. Path, and Therap.," vol. 8. 

3 Berl. klin. Woch. , 1882. p. 533. 



hodgkin's disease. 



155 



despite tlie relative frequency with which the disease is met 
with. 

(II.) Undoubtedly many cases diagnosed as Hodgkin's dis- 
ease are in fact cases of glandular hypertrophy due to syphilis 
or tuberculosis, and this fact has led many to the belief that all 
cases called Hodgkin's disease are in reality only syphilitic or 
tubercular adenitis. In a considerable number of cases, how- 
ever, tuberculosis has been disproven by careful inoculation ex- 
periments with the glandular tissue, and there is no reasonable 
doubt that some cases at any rate are not due to tuberculosis or 
syphilis. Probably the diagnosis can never be made with ab- 
solute certainty during life. 

(III.) The frequent occurrence of fever and other symptoms 
characteristic of an infectious disease has led some writers to 
class it as such. In a certain percentage of cases the disease 
(like leukaemia) has run an acute course, lasting not more than 
six weeks from the first symptom to death. In some chronic 
cases the same sort of evidence of an infectious nature has been 
brought forward. Ulcerations occur in the mouth and intes- 
tine through which morbid products might gain admission. 
Various bacteria (pyogenic and others) have been found in the 
blood and tissues from time to time, but numerous negative 
examinations for micro-organisms are also on record, and the 
evidence is insufficient to establish the infectious nature of the 
disease. IS'one the less, there is a growing tendency among the 
leading writers and observers in Germany and elsewhere, to be- 
lieve that the disease will ultimately be shown to be infectious. 

(lY.) Meantime most surgeons continue to regard it as a 
form of sarcoma and to treat it like malignant disease. 

The Blood. 

Whatever the nature of the disease, we find in the earlier 
stages of most cases normal blood, as will be seen in Table XII. 
(cases 7 to 14 inclusive). 

As the disease progresses the haemoglobin soon begins to 
fall, later the red cells, until, as at the end of Case 10 of the pres- 
ent series, the blood may reach the severest grade of ansemia. 
In acute cases the anaemia may develop very rapidly. The 
usual qualitative changes characterizing severe secondary anae- 
mia may be present. 



156 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table XII.— Hodgkin's Disease. 



Age. 



19 



Adult. 



58 



M. 



Red 
cells. 



5,500,000 

3,848,000 

4,886,000 
5,528,000 
5,160,000 

2,480,000 
5,990,000 

5,440,000 
5,724,000 

3,652,000 



5,210,000 
3,840,000 
1,000,000 
2,820,000 



4,560,000 
4,210,000 
3,800,000 



White 
cells. 



64,000 

39,200 

32,000 
22,200 
25,400 

20,200 
13,500 

9,500 
6,800 

5,800 



5,000 
5,600 



4,800 



4,000 
5,800 
3,332 

1,440 



No 
leucocy- 
tosis. 



Per cent, 
Hasmo- 
globin. 



33 



60 



Remarks. 



Polynuclear, 95 per cent. 
Lymphocytes, 5 " 

Acute, Diff.1500. Adult cells, 95.2 per cent. 

Young " 4.6 " 

Diff. 200 cells. Adult cells, 86.5 percent. 
Six weeks later. Young "12. " 

Eosinophiles, 1.5 " 
Stained specimens normal. 
Adult cells, 95 per cent. 
Young " 5 "• 
Death; autopsy. 
Adult cells, 60 per cent. 



Young 
Diff. 300, 



40 



Adult cells, 50.0 per cent. 
Young " 45.3 
Eosinophiles, 1.3 " 
Myelocytes, 1.7 " 
Big spleen, pallor, nosebleed, debility. 

Two months later. 
Three weeks " 
Adult cells, 80 per cent. 
Young " 17 
Eosinophiles, 3 ' ' 
Re-enti'y. 

^Myelocytes, 1 per cent. Big Uver and spleen. 
Eosinophiles, 4 ' ' 
Diff. 500. Adult cells, 71.25 per cent. 
Young " 28. " 
Eosinophiles, .75 ' ' 
One normoblast. 
Diff. 200. Adult cells, 63.5 per cent. 
Yoimg " 36.5 
Eosinophiles, 1 " 
Many of the lymphocytes have two nuclei. 
Diff. 300. Adult cells, 41.7 per cent. 
Young " 48.4 
Eosinophiles, 9.3 " 
Myelocytes, .6 " 
Diff. 500. Adult cells, 60.2 

Young " 36. " 
Eosinophiles, 5.6 " 
Myelocytes, 2. " 
Two normoblasts. 
Diff. 500. Adult cells, 92. 6 per cent. 
Young 5.2 " 

Myelocytes, 2.2 " 
No eosinophiles. 
Diff. 313. Adult ceUs, 62.3 
Young "37 
Myelocytes, 6 " 



White Cells. 

Wlien inflammation arises in the glandular tumors and some- 
times when none is found, the white cells may be greatly in- 
creased, even up to a ratio of 1 : 80 red cells, as in Case 1 of the 
present series. There is, however, no more resemblance to leu- 
kaemia than in any other form of leucocytosis, the adult cells 
^ Diff. ^Differential count of. 



hodgkin's disease. 



157 



alone being increased. There is no reason for supposing, as 
Keinert ^ does, that relative diminution of the young leucocytes 
is owing to the diseased condition of the lymph glands, for, un- 
less some septic process gets a foothold in the glands, the 
young cells present a normal number or even (as in Case 16) 
considerably increased percentages. 

As in any other cachectic condition, small numbers of mye- 
locytes may be found. They were seen in six of our cases out 
of fourteen in which a color analysis was made, the highest per- 
centage being two per cent. Eosinophils are usually decreased 
when leucocytosis is present. 

Summary. 

Normal blood in early stages. 
Later often marked anaemia. 
Sometimes leucocytosis. 

Diagnostic Value. 

The only help given us by the blood is in excluding leukae- 
mia. Syphilis, tuberculosis, or malignant disease might cause 
similar blood changes or lack of changes. 

^ "Die Zahlung der Blutkorperchen," Berlin, 1891. 



PART II. 

ACUTE INFECTIOUS DISEASES. 



CHAPTEE III. 

INFLUENCE OF FEVER ON THE BLOOD. 

Some of the blood-changes found in acute infections are to 
be regarded as due simply to the fever associated with the dis- 
ease. It is worth while, therefore, to consider what fever per se 
can do to the blood. 

Maragliano ' and others have shown that during fever from 
any cause a contraction of the peripheral vessels occurs. When 
fever disappears, whether spontaneously or from the action of 
antipyretics (phenacetin, quinine, etc.), a dilatation of the ves- 
sels follows. 

FoUomng the laws to which we have so often alluded, the 
contraction of the vessels causes a concentration of the blood 
with rise in specific gravity and in the number of blood cells j^er 
cubic millimetre. This concentration is still further increased 
by the greater loss of water which the organism suffers during 
fever than under normal conditions. 

The effect of these two influences in increasing the number 
of red cells per cubic millimetre is, however, counteracted to a 
considerable extent by the sharing of the blood in the general 
tissue destruction which goes on with increased rapidity during 
fever. Many corpuscles are thus destroyed, but until the tem- 
perature falls the anpemia is covered up by the concentration. 
When the fever leaves the patient there is a sharp fall in the 
number of cells per cubic millimetre, due partly to the destruc- 
tion of corpuscles (hitherto masked by concentration) and parth^ 
to the dilution of tJie blood which is the result of the post-febrile 
dilatation of the peripheral vessels above mentioned. The sud- 
^ Zeit. f. klin. Med., vols. 14 and 17. 



PNEUMONIA. 



159 



denness of tliis fall in the count is proportional to the sudden- 
ness of the fall in temperature. 

The alkalinity of the blood has been often said to be dimin- 
ished in fever, but recent research tends to show t'hat these re- 
sults were obtained by faulty technique, and it is doubtful 
whether the reaction of the blood shows any constant changes 
in fever. 

Leucocytes and fibrin show no constant changes, though in 
the majority of infectious fevers they are increased. 

PNEUMONIA. 

The Blood as a Whole. 

(a) Bacteriology. — The diplococcus lanceolatus has been 
found in the blood of pneumonic patients repeatedly, especially 
in those in whom there has been some secondary diplococcus 
infection {e.g., diplococcus endocarditis); but such findings are 
rare and have generally been in fatal cases with very severe gen- 
eralized infection. 

For example, Sittmann ' out of 16 cases found diplococci in 
the blood of 6, most of which were complicated with lesions in 
other organs, and 4 of which died, while of the 10 whose blood 
was sterile, 9 recovered. 

Boulay found the organism in 2 cases shortly before death. 
Belfanti ^ found it but 6 times out of a large number of cases, 
and of these 6, 5 died. Goldschneider * and Grawitz ' got similar 
results. From these facts it appears that the presence of pneu- 
mococci in the blood is a bad prognostic sign. 

(b) Coagulation is remarkably rapid and in fresh specimens 
the fibrin network is very thick and appears within a few 
minutes. 

(c) In cases with cyanosis the blood is often concentrated at 
the periphery so that its specific gravity is high and the number 
of corpuscles large. 

' Deut. Archiv f. klin. Med. , 1894, p. 333. 
2 Paris Thesis, 1891. 

« Riforma Medica, Naples, 1890, No. 37. 

4 Deut. med. Woch. , 1892, No. 14. 

5 Grawitz : Charite-Annalen, vol. 19. 



160 



SPECIAL PATHOLOGY OF THE BLOOD. 



(d) Monti and Berggriiu ' observed that in children the 
specific gravity was high throughout the course of the disease, 
falling with the temperature. 

Bed Cells. — During the fever the red cells are approximately 
normal (unless increased by cyanosis) ; but after the crisis there 
is often slight anaemia, due partly to the blood destruction evi- 
denced by the frequent presence of hydrobilirubin in the urine 
and the not infrequent occurrence of jaundice. Grawitz con- 
siders also that a general relaxation of the peripheral vessels in 
the post-critical period causes a dilution of the blood with (ap- 
parent) lessening of the red cells. 

Maragliano has noticed " degenerative" changes in the red 
cells in severe cases, but as a rule they do not appear much 
affected either in quantity or quality and our attention is chiefl}' 
directed to the 

White Corpuscles. — 1. Probably as early as the time of the 
chill, and certainly within a few hours after it, the leucocytes 
are greatly increased, and continue so throughout the febrile 
period. 

2. There is no correspondence between the daily variations 
in temperature and the leucocyte curve. In cases in which a 
pseudo-crisis occurs (the temperature falling but quickly rising 
again), the leucocyte count remains high, while at the time of 
the true crisis and often a few hours before it the leucocytes he- 
gin to fall. This fall, however, is hardly ever by "crisis," but 
though starting perhaps a little before the temperature it is one 
to two days longer in reaching normal. When the temperature 
reaches normal by lysis the leucocytes fall with it but generally 
more slowly, and reach normal later. 

3. When resolution is delayed the leucocytosis continues, 
sometimes for weeks, and very gradually sags down to normal 
in cases in which resolution eventually occurs without complica- 
tion. If abscess, empyema, or gangrene follow, the leucocytes 
8tay up. 

4. The degree of leucocytosis is probably the resultant of 
the factors mentioned on page 91, and does not run parallel to 
the degree of fever or the amount of lung involved. Neverthe- 
less cases with extensive signs in both lungs are more apt to 
have very high counts, provided the " reaction" of the patient 

^ Arch. f. Kinderheilk., vol. 17. 



PNEUMONIA. 



161 



against the infection is vigorous. The cases appear to fall 
into tlie following groups as regards the degree of leucocytosis 
present. 

1. Mild infection, vigorous reaction = slight leucocytosis. 
3. Severe or moderate infection, vigorous reaction = marked 
leucocytosis. 

3. Severe infection, feeble reaction = no leucocytosis. 

(a) The cases in Class 1 all recover, but they are very few 
in number, (h) Those in Class 2, which includes over nine- 
tenths of all cases, may or may not recover, according as the 
fight between patient and disease comes out one way or the 
other. 

(c) Class 3 almost invariably die ; there is not sufficient of a 
struggle to raise the leucocyte -count. 

Where either the patient or his disease easily gains the 
mastery there is no leucocytosis or a very slight one; but in 
the much larger class of cases in which the struggle is a fierce 
one, leucocytosis appears, lohichever ivay the struggle results. 

Pick ^ noted that pneumonia complicating cases of small-pox 
which were already very sick, caused no leucocytosis, and the 
same is often true in those whose power of resistance is reduced 
by age, alcoholism, typhoid, or by some chronic disease. 

Yon Jaksch, noticing the fatality of cases without leucocy- 
tosis, suggested that we should induce leucocytosis by inject- 
ing turpentine or other irritants so as to cause abscess; but 
this has not proved of any benefit to the patient, nor has 
the production of leucocytosis without abscess, as can be 
done with pilocarpine or nuclein, been any more successful. 
There is no difficulty in producing the leucocytosis by these 
means, but all observers are agreed that it does the patients 
no good. 

Leucocytosis is checked by antipyretics (Hare^) but not by 
cold bathing, which speaks in favor of the latter method of re- 
ducing temperature. 

The general course of the leucocytes is seen in the accom- 
panying charts from Billings, to whose excellent article I am 
greatly indebted. 

' Arch. f. Dermat. undSyph., vol. 25, p. &3. 
2 New York Medical Record, May 9th, 1896. 



162 



SPECIAL PATHOLOGY OF THE BLOOD. 



Chart I.— Pneumonia, Showing Fall by Crisis (Billings). 

Feb. \ 16 \ 17 \ 18 \ 19 \ 20 \ n \ 22 \ 



a ^ m i 




s < 




; 1 


i 6 m e f 


ft 6 n 




J f 


s < 




n /2 6 m € f9 e m g » 


106" 




















































































































/05° 
































































































































































































\ 








































103° 


















\ 


































































































102° 














-T 

; 




























































p 










































101° 




















































































































100° 




















































































































99° 


































/ 
























98" 
























v. 




















































_. 
















.... 
















































































50,000 
















































































































































































-\ 


















































140,000 


























































































































\ 
















































ililiiill 1 










V 
























































































































































































































































































































































































































































































































































































































































































































































































































































4,000 
3.000 
















































































































i 








































1 













The upper chart shows the course of the temperature, the lower that of 

the leucocytes. 

Qualitative Changes. — As in most forms of leucocytosis the 
adult leucocytes are enormouslj^ increased, often making over 
ninety per cent of all the white cells. Eosinophils and blood 
plates disappear and the young forms are much reduced. After 
the crisis this is reversed, the adult forms falling often below 
sixty per cent, while the eosinophiles and blood plates are above 
normal. As to the differential count in the (fatal) cases in which 



PNEUMONIA. 



103 



Chart II. — Pneumonia and Rheumatism, 

May. June. 























































































































/OS" 




















































































































m" 


























































103° 


■4- 
















































































































102° 






\ 
























































I 


























_ 


























101° 






J 












































































































100° 




























































































• 




















[f- 


99° 


















































































































98° 


■"■ 




















\J 
-• 




^— 




>i 












■#- 




-V 




V 














97° 


















































































































50.000 

80.000 
18,000 
16,000 
14,000 
13,000 
10,000 
8,000 
6,000 






















































































P 
























































</ 
























































c 






















































































/ 




























































































\ 
















































F 










\ 


























































\ 
































/ 














































































































































































































4.000 
3,000- 








































































































































































i 



The upper chart shows the course of the temperature, the lower that of 

the leucocytes. 

leucocytosis is absent, data are scanty. Bieganski thouglit tlie 
adult varieties decreased, Rieder found them increased, wliile 
Billings finds them normal. No general law can be stated on 
this point as yet. 

In one remarkable case occurring at the Massachusetts 
General Hospital in 1894, the conditions were entirely different 
form those just stated. The patient, a girl of six, had at en- 
trance 72,100 leucocytes per cubic millimetre. Two days after 
the count was 94,600. A differential count made at the same 
time showed that the small lymphocytes made up sixty-six per 
cent of all the 94,600 leucocytes per cubic millimetre. The 
adult cells were reduced to thirty per cent. Lymphatic leu- 
kaemia was thought of, but the leucocytosis was gone in ten 



164 



SPECIAL PATHOLOGY OF THE BLOOD. 



days and within a fortnight the patient left the hospital well. 
I have seen one reference to such a condition. "In a certain 
number of cases the leucocytosis is characterized by the great 
number of the youngest forms of leucocytes. This condition 
persists during convalescence." ^ 

Diagnostic and Prognostic Value. 

1. In cases of so-called '^central pneumonia'' in which the 
symptoms but not the physical signs of the disease are manifest, 
the presence of a well-marked leucocytosis is often of great diag- 
nostic value. It excludes malaria, typhoid, and uncomplicated 
grippe as causes of fever, and if scarlet fever and suppuration 
can be excluded by other evidence, it makes pneumonia very 
probable. 

I have repeatedly seen the diagnosis of pneumonia made in 
the absence of physical signs and largely on the evidence of the 
blood count, the diagnosis being confirmed several days later by 
the appearance of typical signs of consolidation. In a case of 
Dr. F. C. Shattuck's, sick five days, yet showing no signs of 
consolidation of the lung, the presence of a marked leucocytosis 
excluded typhoid, the only other likely diagnosis, and led Dr. 
Shattuck to treat the case as pneumonia, the wisdom of which 
course was later demonstrated by the appearance of signs of 
consolidation. 

2. Between pneumonia and capillary bronchitis the condition 
of the blood is of no help, as the latter also causes leucocytosis, 
and some cases affecting the larger tubes do the same. 

3. In cases of pneumonia occurring in very old or very 
young people, in which the fever and symptoms maj^ be very 
slight, the presence of leucocytosis may be the first thing to 
direct our attention to the lungs, dyspnoea and cough being ab- 
sent. 

J-ii. prognosis, the important point is that tlie absence of leu- 
cocytosis is a very had sign, loMle its presence is neither good 
nor had. It must be remembered also that in the very mildest 
cases we may find the same absence of leucocytosis. which in 
any other but the mildest would be almost surely fatal. 

' Stienon : Jour, de Med., de Chirurg. et de Pharm., Bruxelles, 1895, 
t. iv. , fasc. 1. 



TYPHOID FEVER. 



165 



This last point, wliicli apxjears to me of great importance, is 
illustrated by the following figures : 

Halla reported 14 cases ; 2 had no leucocytosis, and both died. 

Billings reported 22 cases; 1 had no leucocytosis and died. 

Laehr with 16 cases, and Bieder with 26, got similar results. 

Ewing in 101 cases found leucocytosis absent in 6 ; 6 died. 

Von Jaksch and Kilodse likewise maintain that the absence 
of leucocytosis is usually fatal. 

In the Massachusetts General Hospital 229 cases have been 
studied. In general they entirely confirm the results obtained 
by Billings and summarized above; 18 of these presented no 
leucocytosis at any time, and of these 18, 17 died and the other 
one seemed moribund but finally recovered. 

The evidence, therefore, is overwhelmingly in favor of the 
view that where leucocytosis is absent in any but the mildest 
cases the prognosis is almost fatal. The presence of leucocyto- 
sis, on the other hand, is no guaranty whatever of a favorable 
issue. 

The series of cases at the Massachusetts Hospital is too 
large to exhibit in tabular form. Their results may be sum- 
marized as follows : 

Cases with leucocytosis between 10,000 to 15,000 = 24 

15,000 " 20,000 = 49 
20,000 " 25,000 = 46 
25,000 " 30,000 = 31 
30,000 " 35,000 = 19 
35,000 " 40,000 = 4 
" ^' " 40,000 " 45,000 = 7 

45,000 " 50,000 = 2 
50,000 " 55,000 = 4 
" " " but not accurately counted = 43 

Average = 24, 000 + 229 



TYPHOID FEVER. 
Bacteriology. 

Although the bacilli of Eberth are occasionally to be found 
in the blood by culture, it is only in the most marked cases that 
they occur, and then but rarely, so that at present we derive no 
help in doubtful cases by the bacteriological examination of the 
blood. 



166 



SPECIAL PATHOLOGY OF THE BLOOD. 



Toward the end of the disease, wheu the temperature is apt 
to be very irregular (so-called " period of steep curves"), pyogenic 
cocci are occasionally to be found in cultures made from the 
blood, and doubtless account for many of the recrudescences and 
temporary febrile attacks, with or without chills, which are so , 
common in early convalescence. 

The Blood as a Whole. — 1. Coagulation and fibrin are 
normal. 

2. Specific gravity follows the course of the haemoglobin. 

3. The general effects of fever (see above, page 158) are in 
part accountable for the changes next to be described, while 
some of them are more peculiar to typhoid fever. 

Bed Cells. — During the first two weeks there are no consid- 
erable changes, except in so far as a certain amount of concen- 
tration of the blood with apparent increase of cells may be 
brought about by diarrhoea or sweating. Baths have a like 
effect if the blood is examined just after the immersion.' In 
the third week the red cells usually begin to decrease and in ex- 
treme cases may get as low as 1,300,000 at the beginning of con- 
valescence — i.e., when body weight begins to increase. Hayem 
considers that the diminution begins rather suddenly in the 
middle or end of the third week of severe cases, but according 
to Thayer the diminution is gradual, though at first slight, grow- 
ing more rapid at the time of defervescence, and continuing 
often into convalescence. The lowest point is reached about the 
first week of convalescence. 

The following figures (Thayer) illustrate this. 

First week, Second week, Third week, Fourth week, Fifth week, Sixth week. 
2 counts. 10 counts. 9 counts. 6 counts. 7 counts. 

5,636,000 4,960,599 4.951.535 4,038,333 3,856,786 4,364,250 

His later counts show a gradual increase. He finds that the 
amount of anaemia bears, as a rule, a direct relation to the 
severity of the case, but in one of his cases a grave anaemia 
(1,300,000) followed a mild attack. " The anaemia may be severe 
enough to form of itself a dangerous complication of the proc- 
ess." 

Hcemoglohin . — The loss of coloring matter roughly parallels 
that of the red cells, but is always relatively greater and is 
slower in reaching normal. 

' Aiitipyrin and acetanilid have no effects on the red cells. 



TYPHOID FEVER. 



167 



Leucocytes. — The absence of any increase of the white cells 
is the most important point. 

Starting with an approximately normal count, the number 
falls during the fever, often below 2,000, according to Hay em, 
and sometimes below 1,000 per cubic millimetre. Khetagurow 
finds the lowest counts (2,500-3,000) about the end of the third 
week. 

Thayer's figures are as follows: » 

First week, Second week, Third week, Fourth week. Fifth week, Sixth week, 
21 counts. 50 counts. 40 counts. 28 counts. 16 counts. 5 counts. 

6,984 6,468 6,260 5,877 6.621 7,000 

In the two hundred and ninety-two cases counted at the 
Massachusetts General Hospital, the course of the leucocytes 
has unfortunately not been followed by weeks with sufficient 
accuracy to make comparisons of value. In a general way, 
however, they corroborate all of Thayer's positions. At the be- 
ginning of the cases the count was often high (11,000), owing 
probably to concentration of the blood by starvation and diar- 
rhoea. The high count of red cells confirmed this, the ratio of 
Ted to white remaining normal. The counts of leucocytes then 
gradually diminished, as in Thayer's cases. 

The range of the counts was as follows: 



Between 


1,000 and 2,000 = 


7 


cases. 




2,000 " 


3,000 = 


25 


a 




3,000 " 


4,000 = 


28 






4,000 " 


5,000 = 


52 




(( 


5,000 " 


6,000 = 


44 


11 




6,000 " 


7,000 = 


50 






7,000 " 


8,000 = 


28 


u 




8,000 " 


9,000 = 


25 






9,000 " 


10,000 = 


22 






10, 000 " 


11,000 = 


7 




Over 


11,000 




4 





292 cases. 



From these figures I have excluded all cases counted only 
under circumstances likely to concentrate the blood (cyanosis, 
after baths, after severe diarrhoea) . 

There is no doubt that leucocytosis does occasionally occur 
when no complication exists so far as toe can ascertain during 
life. The four cases over 11,000 (see the above table) were all 



168 



SPECIAL PATHOLOGY OF THE BLOOD. 



counted repeatedly and complications were carefully sought for, 
but none were found. The most striking case showed the fol- 
lowing counts : 

October 3d 13.100 

4th 13,000 

5th 16,500 

7th 13.300 

8th 11/200 

10th 10.600 

13th 13.500 

loth 17,700 

" 17th 15,500, death ; autopsy. 

The autopsy showed typical typhoid lesions and nothing 
else.' Another and much milder case showed 11, 000-12. OCK) 
white cells constantly for over two weeks, and no cause could be 
found to account for it. 

The great rarity of such cases and constant association of 
leucocytosis with any of the numerous complications which we 
can recognize, rather inclines me to the belief that in all the 
cases in which leucocytosis exists constantly, some complication 
really is present though imi'e cognized. The possibility of a 
secondary septic infection, of an osteomyelitis, or phlebitis of 
internal veins cannot be excluded without fuither evidence. 

Examples of the effect of complications are as follows : 
Perforation. — Case 1. {a) Five days before perforation. 8,300 
{Id) At time of the perforation, . 24,000 
Case n. At time of perforation, . . 18,500 
FJiIehiti^. —C&se I. («) Two days before onset, . . 6,400 
(h) At time of the onset, . . . 12,900 
(c) One week later, .... 10.100 
Case XL (a) One week before onset, . . 4.800 
(5) At time of onset, .... 16,200 

Otitis Jledia.—CsiQe I. {a) At entrance, 5,300 

[h) Mastoid abscess, .... 16,400 

Case n. (a) At entrance. 8.400 

{h) Two weeks later, after open- 
ing di^um membrane 
(sero-pu r u 1 e n t d i s- 

charge>, 11.200 

' Thrombosis of internal veins and osteomyelitis were not carefully 
searched for at autopsy and may have existed. 



TYPHOID FEVER. 



169 



Casein. («) At entrance, . . . . . 7,320 
(h) Otitis, 14,000 

A freely discharging otitis soon ceases to cause leucocytosis, 
e.g., a case of serous otitis media seven days after puncture, 
but still freel}^ discharged, showed but 5,320 white cells per 
cubic millimetre. 

An abscess of the buttock raised the count from 8,000 to 
11,200, and a hemorrhage from 8,000 to 11,300. 

General bronchitis has usually no effect in augmenting the 
leucocyte count unless the disease invades the smallest tubes 
(capillary bronchitis) . Thus tw^o cases of this affection showed 
9,000 and 8,000 leucocj tes respectively. 

Cystitis had no effect in two cases. 

In two cases whose symptoms simulated otitis (deafness, 
rise of temperature, pain in the head, and in one a convulsion) 
but whose blood counts were normal, the trouble turned out to 
be functional and nothing came of it, the symptoms disappear- 
ing within twenty-four hours. 

Some observers ' have noted a slight leucocytosis at the be- 
ginning of convalescence. Thayer did not find this, and I have 
been equally unsuccessful. 

It occasionally happens in very exhausted patients that com- 
plications fail to produce any leucocytosis, the patient (as in 
some fatal cases of pneumonia or purulent peritonitis) being 
unable to react against the infection. For example, I have seen 
a large ischio-rectal abscess develop in a moribund typhoid 
patient without producing an}^ effect on the leucocyte count. 
Yon Limbeck has noticed the same lack of reaction in typhoid 
patients after a hemorrhage and bronchopneumonia, and Kieder 
in croupous pneumonia occurring as a complication. 

These cases, however, are exceptional, and in many of them 
the percentage of adult leucocytes rises, though no increase in 
the total leucocyte count is present. This increased percentage 
of adult forms generally betrays the presence of the complica- 
tion, since during most of the disease (if uncomplicated) the 
adult :Cprms are diminished. 

In normal cases the blood begins to return to normal as: 

^ E.g., Aporti and Radaeli (11th Congress for Medical Science, Rome^ 
March 29th, 1894). 
12 



170 



SPECIAL PATHOLOGY OF THE BLOOD. 



soon as the fever is gone and reaches the normal in the sixth or 
seventh week. 

Qualitative Changes. 

Red Cells. — The condition is either normal or shows the 
changes common to all varieties of secondary anaemia. 

Wliite Cells. — All observers are agreed upon the following 
changes : 

1. The adult cells i)rogressiveh' diminish with a corre- 
sponding increase in the young cells. This change is but slight 
in the first two weeks, but grows marked in the latter part of the 
illness, the adult cells falling below fifty per cent. Among the 
young cells the larger forms predominate. 

2. It is not until after the disappearance of fever (from three 
to ten days after it, according to Ouskow) that the adult cells 
begin to increase again and their normal percentage is not 
reached untill the tenth or eleventh week. Thayer's differential 
counts show: 

Second week, Third week, Fourth week, Fifth week. Sixth week, 

5 counts. 1 count. 3 counts. 1 count. 2 counts. 

71. 7 per cent. 66. 5 per cent. 65. 3 per cent. 58. 5 per cent. 53. 4 per cent. 

3. Eosinophiles are present in small numbers. 

Summary. 

1. Post-febrile anaemia, sometimes very intense. 

2. No leucocytosis ; in late weeks leucopenia. 

3. Increased percentage of young leucocytes at the expense 
of adult forms, especially marked in later weeks. 

4. Most complications cause leucocytosis. 

Diagnostic Value. 

There are few diseases (outside of those known as diseases 
of the blood itself) in which the blood count is so often of value in 
diagnosis. The diagnosis of typhoid fever is to be made by ex- 
clusion — exclusion of other causes of fever and of local inflam- 
matory processes in particular. 

1. Now in this process of exclusion, the blood is a most 
powerful adjuvant, inasmuch as almost all local infiammatory 
2Jrocesses have leucocytosis, ivhile typhoid (uncomplicated) does not. 



TYPHOID FEVER. 



171 



1 have seen two cases in which the chart and symptoms pointed 
to typhoid but in which the persistent marked leucocytosis 
directed attention to the search for an inflammatory focus. Both 
were at first unattended with pain, tenderness, or other localiz- 
ing symptom, but later signs and symptoms began to point to 
the liver, from which pus was evacuated by puncture. These 
cases of abscess of the liver are typical of the value of blood ex- 
amination for any deep-seated suppuration. I have seen good 
clinicians puzzled for twenty -four hours over the diagnosis be- 
tween appendicitis and typhoid, but the indication of the blood 
count was always fulfilled. All pygemic or septicsemic processes 
are distinguishable from typhoid by the same test — the pres- 
ence of leucocytosis in the former. 

Of the value of the blood in distinguishing certain cases of 
pneumonia from typhoid I have already spoken on page 165. 

2. Aside from local or general pyogenic infections perhaps 
the disease most often confounded with typhoid is malaria. 
This is especially the case in the southern part of this country, 
where for want of proper blood examination the confusion of the 
two diseases is indicated in such a term as " typho-malarial 
fever." Malaria and typhoid are alike in having no leucocy- 
tosis, but the presence of the malarial parasite is an absolute 
test and in marked cases is always decisive. Very mild cases 
of malaria may show so few organisms in the peripheral circu- 
lation that without prolonged search they cannot be found, and 
in the severest types of all, the organisms are not very abun- 
dant. In the vast majority of cases, however, the organism can 
be readily found and our diagnosis made certain. 

3. Tuberculosis, if uncomiDlicated by any pyogenic organ- 
isms, cannot be distinguished from typhoid by the examination 
of the blood alone, as neither disease shows leucocytosis. 

A large proportion of young leucocytes is commoner in 
typhoid than in tuberculosis, but it may occur in either disease. 
In the majority of cases, however, tuberculosis is complicated 
with septicaemia from a secondary pyogenic infection, and is 
then easily distinguished by the existence of leucocytosis. 

4. Typhus fever has not been well studied and the reports of 
its blood condition are contradictory. At present we cannot 
say whether or not it can be distinguished from typhoid by the 
blood examination. 



SPECIAL PATHOLOGY OF THE BLOOD. 



The occurrence of complications in typhoid may mask its 
characteristic blood changes so as to make the blood useless in 
diagnosis ; but in most early cases, in which the diagnosis is es- 
pecially important and difficult, the blood shows no leucocytosis 
and is therefore of great value in the exclusion of other diseases. 

DIPHTHERIA. 

Bacilli of diphtheria in the circulating blood are practically 
never to be found. 

The specific gravity, according to Grawitz, is above normal at 
the height of the disease. He obtained the same result experi- 
mentally by injecting cultures of the Klebs-Loffler bacillus 
into dogs and rabbits. He concludes that the poison of the 
disease is lymphagogic and so concentrates the blood. 

Bed Corpuscles. — Morse's' investigations show an average of 
5,100,000 in twenty cases counted during the first week of the 
disease and of 5,150,000 in 10 cases during the second and third 
week of the disease — practically normal figures. 

These are the first systematic ' investigations of the red cells 
in diphtheria and are confii-med by the reports of Ewing, Engel, 
and Billings. The latter observer in counts made in seven cases 
during the first five days of illness found an average of 5,600,- 
000+ red cells per cubic millimetre. During the first five to ten 
days after this, the same cases showed an average loss of 510,000 
cells per cubic millimetre ; five out of the seven showing consid- 
erable losses, two remaining about the same. These were cases 
treated without antitoxin. The two cases showing no loss of 
red cells were both very mild, one having no membrane at any 
time. The diminution ranged from 470,000 (third day) to 
2,040,000 (sixth day). As a rule no diminution can be made 
out until after the third or fourth day. 

Out of twenty-three cases treated with antitoxin and each 
counted several times over, only three showed any considerable 
diminution in the red cells and these lost less than 400,000 
each, not much beyond the limit of error (200,000) allowed for 
by the investigator, and all of them severe cases. Six patients 
who were anaemic when admitted (average =4, 640, 000) showed a 

^ Boston jMedical and Suroical Journal. IMarch Tth, 1895. 
- Earlier reports are faulty as to technique. 



DIPHTHERIA. 



173 



steady rise in the red cells as tlie disease (treated with anti- 
toxin) progressed. 

It is evident from these figures that antitoxin largely pre- 
vents the anaemia which usually develops in the first five to ten 
days. In cases not treated with antitoxin the regeneration 
from the resulting anaemia is slow. Healthy individuals in- 
jected with antitoxin showed a very moderate reduction in the 
red cells in about one-half the cases, the greatest loss being 932,- 
000 per cubic millimetre (fifteen cases counted hj Billings) . 

Qualitative Changes. — Billings' careful study of stained speci- 
mens showed no deformities in size or shape and no nucleated 
red cells. Polychromatophilic red corpuscles were very few in 
the cases in which antitoxin was used, but more numerous where 
it was not used. 

Scemoglohin. — Here again the most thorough investigations 
are those of Billings. In cases treated without antitoxin there 
was an average loss of ten per cent, regained in part during con- 
valescence, but as usual reaching normal later than the count 
of corpuscles. When antitoxin was given, the diminution of 
haemoglobin was less marked, but where the decrease did occur 
the return to normal was slow compared to that of the red cells, 
even when the patients were up and about and apparently well. 

White Corpuscles. — Leaving out the older observations in 
which the technique was probably faulty, the principal investi- 
gators are Morse, Ewing, Gabritschewsky, and Billings. 

All agree that a considerable leucocytosis is present in most 
cases — 34 out of 36 of Billings' cases, 26 out of 30 of Morse's (the 
latter made but one count in each case), 49 out of 53 of Ewing's. 
In a general way, the severest cases show the greatest leucocy- 
tosis, but it does not follow the pulse, temperature, nor the ex- 
tent of the membrane, and " the ordinary clinical examination 
of the patient is of much greater value in . . . prognosis . . . 
than any information to be gained from the examination of the 
blood. The latter is simply confirmatory, never indispensable" 
(Billings). Morse's conclusions are the same, although he con- 
siders that with notable exceptions the amount of membrane is 
a rough measure of the degree of leucocytosis. He finds no 
correspondence between the glandular swellings and the degree 
of leucocytosis, though he noted that " in the fatal 'septic' cases 
with greatly enlarged glands," very high counts were present. 



174 



SPECIAL PATHOLOGY OF THE BLOOD. 



Other cases with little or no enlargement of glands showed 
equally high counts, however. 

Ewing's 4 cases without leucocytosis were all mild, but of 
Billings' 2 cases without leucocytosis one was the severest of 
his whole series, while the other was mild. Of Morse's 4 cases 
without leucocytosis 3 were mild and 1 severe. Gabritschew- 
sky's 14 cases all showed leucocytosis. 

Putting the results of these four observers together we see 
that when leucocytosis is absent the cases are either very mild 
or very severe, conditions analogous to those to be noted in pneu- 
monia and septicaemia. The counts in recent epidemics range 
from normal to 48,000 (Morse) or to 38,600 (Billings). Felsen- 
thal ^ found 148,229 per cubic millimetre in one case, and 
Bouchut's^ counts are often over 75,000. 

In a general way the counts rise while the disease progresses 
and fall gradually as improvement goes on, disappearing after 
the membrane. " The leucocytosis is well marked by the third 
day and very likely earlier" (Morse). Billings found an in- 
crease after one day's illness, but usually less than was present 
later in the disease; one of his cases, however, had a higher count 
on the first day of the disease than on any subsequent day, 
though no antitoxin was given. 

The injection of antitoxin has apparently no effect upon 
the leucocyte count (strange to say) except in the first twenty- 
four hours after its use. Immediately^, i.e., within thirty min- 
utes after an injection, the leucocytes are stated by Ewing 
to be considerably diminished, but the leucocyte curve does 
not reach normal any sooner than in cases in which no anti- 
toxin is given, although it begins to fall in the majority of cases 
after the injection. The same thing (according to Billings) 
takes place without antitoxin. 

The leucocytes of healthy persons are likewise unaffected 
by antitoxin injections. 

Qualitative Changes. — All authors agree that in most cases 
the adult forms are increased. Morse found an average of 80 
per cent in 26 of his 30 cases. Of the other 4, 1 was normal 
and 3 subnormal (58, 59, and 59 per cent) ; 2 of these were con- 

' Archiv f. Kinderheilk., vol. xv., p. 78, 1893. 
2 Comptes Rendas, 1877, Ixxv., No. 3. 



DIPHTHERIA. 



175 



valescent, the other had been sick a week and had 12,000 white 
cells per cubic millimetre. A similar lymphocytosis was present 
in 1 of Ewing's 53 cases, and in 1 of Eieder's during convales- 
cence. Billings thinks such a lymphocytosis may be present 
in perfect health, mentioning cases with 32, 33, and 35 per cent 
of small lymphocytes in sound persons. Such a condition did 
not occur in any of his diphtheritic cases except in the single 
fatal case without leucocytosis. Here the adult cells were re- 
duced to 55 per cent and the lymphocytes (large and small) 
made up the remaining 45 per cent, 28 per cent being large 
forms.' In the rest of his cases the adult varieties averaged 80 
per cent and the young forms 19 per cent, the eosinophils 
being reduced to 1 per cent on the average and often being en- 
tirely absent. With Morse eosinophils averaged 2 per cent. 

The proportion of adult cells is usually directly proportional 
to the total increase of leucocytes. 

Ewing thinks that " the staining reaction of the leucocytes is 
an accurate measure of the severity of the diphtheritic infec- 
tion," and this staining reaction he finds increased in favorable 
cases by the injection of antitoxin. 

Billings did not find am^ such changes in " staining reaction," 
though he carefully followed out Ewing's procedures. 

Engel ^ found that antitoxin at first slightly increased the 
percentage of young leucocytes, and sometimes this increase 
was very marked. In one case the young forms increased from 
twenty-four to sixty-five per cent after antitoxin. 

The point on which he specially insists is the presence of 
considerable numbers of myelocytes in fatal cases. 

Of the 32 cases examined by him 15 died, and 7 of these had 
from 3.6 to 16.8 per cent of myelocytes in every one hundred 
leucocytes. Myelocytes were also present in some of the cases 
which recovered, but in smaller numbers (1.3 to 1.5 per cent.) 

In one case he found on the third day of the disease 4.3 per 
cent of myelocytes, and from this point the percentage gradually 
rose to 13.8 per cent, and then fell, there being 1.7 per cent 
present at the time of death. An abscess occurring in the case 

^ In Eieder's case above referred to, aged three years, the young cells 
rose from nineteen per cent during the fever to sixty-four per cent in 
convalescence. 

^Soc. f. inner. Med., Berlin, July 6th, 1896. 



176 



SPECIAL PATHOLOGY OF THE BLOOD. 



showed only tlie usual adult leucocytes (polymorpliouuclear) in 
its contents. He concluded that a large percentage of myelo- 
cytes is a bad prognostic sign in any case. 

Myelocytes are not mentioned in any of the numerous differ- 
ential counts made by Gabritschewsky, Ewing, Morse, and Bill- 
ings, so that Engel's observation is so far unique. 

Summary, 

1. Moderate anaemia, especially in cases treated without an- 
titoxin. Kegeueration is slow. 

2. Leucocytosis, very roughly parallel to the severity of the 
disease, unaffected by antitoxin treatment, gradually decreas- 
ing as the disease passes off, sometimes absent in very mild or 
very severe cases. 

3. xldult leucocytes much increased during febrile stages, 
often diminished in convalescence. 

4. Myelocytes numerous in some severe cases. 

The blood examination has no diagnostic value so far as I 
can see ; in prognosis the absence of leucocytosis (except in ob- 
Tiously mild cases) and the presence of many myelocytes are ap- 
parently bad signs. 



CHAPTEE IV. 



ACUTE INFECTIOUS DISEASES (CONTINUED). 
SCARLET FEVER. 

Heubner* noted hsemoglobinsemia in one case. Fibrin is 
not increased even at the height of the fever, provided inflam- 
matory complications are absent. 

Bed Cells. — Very little is to be found in literature upon the 
subject. Kotschetkoff ^ noted a gradual diminution of the red 
cells to about 3,000,000, regeneration taking place in the course 
of not less than six weeks. Other observers have found little 
or no anaemia. 

Hay em ^ estimates the average loss of red cells at 1,000,000. 
In mild cases he finds the lowest figures on the first day of 
normal temperature. In severer cases in which the fever comes 
down slowly, the red cells may not reach their minimum till 
twenty-four hours after reaching the normal temperature. 

FelsenthaP in six cases found the count to be 4,500,000 to 
5,500,000 — no considerable variation from normal. 

Zappert ' in six cases found it to be from 3,920,000 to 4,- 
500,000, an average of 4,150,000. 

White Cells. — Most observers are agreed that leucocytosis is 
the rule, contrasting in this respect with measles, in which no 
leucocytosis occurs. The increase may be present even six days 
before the rash appears and attains its maximum two or three 
days after the eruption. In light cases it may sink to normal 
even before the fever is gone, while in severer cases it may per- 
sist several days after a normal temperature is reached. Von 
Limbeck had a case in which the leucocytosis persisted for 

1 Deut. Arch. f. klin. Med., vol. 23. 

2 Ref . in Petersburg, med. Woch., 1893, 1. 
^ Loc. cit. , p. 914. 

4 Arch. f. Kinderheilk., 1892, p. 80. 

5 Zeit. f. klin. Med., 1893, p. 292. 



178 



SPECIAL PATHOLOGY OF THE BLOOD. 



twelve days after the temperature had become normal. Forty 
thousand per cubic millimetre is not unusual in well-marked 
cases. Eieder's ten cases averaged 17,500; Felsenthal's six 
counts were between 18,000 and 30,000. 

In a general way the severest cases are apt to have the high- 
est leucocyte counts ; the figures have no direct relation to the 
amount of fever, glandular swelling, or to complications in the 
ear or kidney. 

Qualitative Changes. — The adult forms are increased, often 
to ninety per cent, soon falling except in the worst cases. The 
peculiar characteristic of the disease is the persistence of eosino- 
philes in all but the severest cases despite the increase of adult 
forms. They may run as high as five per cent during the fever, 
and are still more numerous in convalescence, remaining in- 
creased for six weeks. According to Kotschetkoff, disappear- 
ance of eosinophiles is a bad prognostic sign except at the very 
beginning of the fever, when they may be temporarily absent in 
favorable cases. Presumably they have some connection with 
the exanthem, eosinophilia being so common in connection with 
skin lesions. They may number fifteen per cent of the leuco- 
cytes in convalescence. Felsenthal's average is five per cent. ; 
Zappert's, three per cent. The young cells are decreased pro- 
portionately to the severity of the case, the worst cases showing 
only two to four per cent. 

An increase of eosinophiles during a scarlatinal nephritis is 
regarded by Neusser and his pupils as a favorable sign, and their 
absence as ominous. In ordinary cases without nephritis they 
reach their maximum in the second or third week and are not 
normal till the sixth. 

Summary. 

Moderate anaemia. 

Leucocytosis beginning before the eruption and often lasting 
into convalescence. 

Eosinophiles increased in favorable cases, absent in bad 
cases. 

Diagnostic and Prognostic Value. 

1. The chief importance of the blood examination is in dis- 
tinguishing the disease from measles and the eruptions of other 
diseases. Measles has no leucocytosis. 



MEASLES. 



179 



2. Whether the prognostic significance attached by Neusser 
and others to the percentage of eosinophils is genuine or not 
cannot as yet be positively stated. . 

MEASLES. 

In mild cases the blood shows no changes at all. Where 
bronchitis, coryza, and conjunctivitis are very marked, fibrin 
may be increased. 

Red Cells. — In mild cases no change — never over 400,000 or 
500,000 red cells are lost (Hayem). Felsenthal's eight cases 
showed counts of 5,000,000 to 5,500,000. 

White Cells. — In most cases there is no increase. Felsenthal 
in eight cases found the count normal or diminished. Pee 
found but 4,000 in a case with a fever of 102.7°. Eieder's eight 
cases averaged 7,500, being loivest at the height of the disease 
and increasing as fever passed off. Complication with catarrhal 
pneumonia or a very bad bronchitis and coryza may slightly 
raise the count. The eosinophiles, contrary to the example of 
scarlet fever, are often absent during fever. 

The Massachusetts Hospital records furnish the following 
counts : 





Red cells. 


White cells. 


Percentage 
haemoglobin. 


Remarks. 


Case 1 


5, 000, boo 

4,700,000 


6,000 
6,500 
7,000 
9,000 


'60' 

65 


Eruption out 1 day. 

" " 3 clays. 

" just out. 
Petechial eruption 
("black measles"). 


" 2 


" 3 


" 4 





Felsenthal found the adult cells much increased and eosino- 
philes never over one per cent. I have seen no other full differ- 
ential counts in the disease. The value of the blood examina- 
tion is considerable in excluding scarlet fever, diphtheria, and 
syphilitic roseola, all of which show leucocytosis. It cannot 
apparently be distinguished by the blood count from Rotheln 
(German measles) in two cases of which, seen at the Massa- 
chusetts Hospital, the white cells were 6,000 and 8,000 respec- 
tively. 

A single case of mumps showed no leucocytosis. 



180 



SPECIAL PATHOLOGY OF THE BLOOD. 



SMALL-POX (VARIOLA). 

Red Cells. — According to Hay em no other fever Is so de- 
structive of red cells. During the fever the count is normal or 
increased, but when the temperature falls permanently the num- 
ber of red cells falls suddenly, whether because the blood is 
diluted (see above, page 158) or by a real destruction. From 
this time on the cells are slowly regenerated; even at the 
fifteenth day Hayem found them considerably below normal. 

In hemorrhagic cases the anaemia comes on more quickly, 
its degree depending on the amount of hemorrhage. In one 
case, dying on the seventh day of the eruption, Hayem found 
but 2,000,000 red cells, in another at the same stage, 4,600,000. 

Fibrin is not increased until the stage of suppuration is 
reached. 

White Corjjuscles. — Pick, who carefully studied 42 cases, 
found that the very lightest cases, such as occur in vaccinated 
persons, may cause no leucocytosis. In a woman of twenty- 
two on the third day of illness with a temperature of 105°, the 
count was only 4,200 and on the fifth day (temperature 99°) 
3,600. This patient had been vaccinated. 

Severe cases if without complication show no leucocytosis 
till the pus appears in the vesicles, and after this period the leu- 
cocytosis slowlj' sinks again. For example, on the fifth day of 
the illness, leucocytes 4,200; at the beginning of suppuration, 
11,600 (eighth day); at the height of suppuration (tenth day), 
17,200; at the thirteenth day, pustules drying up, leucocytes 
7,600. 

In the severest types, the leucocytes follow about the same 
course, there being no leucocytosis whatever in the initial or 
eruptive stages. Only when the infection with pus organisms 
begins do the leucocytes rise, the poison of variola itself having 
apparently no tendency to increase the count. The amount and 
duration of the increase at the stage of suppuration is in a gen- 
eral way proportional to the severity of the case. 

ACUTE ARTICULAR RHEUMATISM. 

According to Hayem and Garrod ' the blood constitutes as in 
syphilis a most valuable measure of the intensity of the sickness, 
^ British Medical Journal, May 28th, 1893. 



ACUTE ARTICULAR RHEUMATISM. 



181 



which is parallel to the severity of the blood-changesr rather 
than to the number of joints affected. The fever, the intensity 
of the lesions, and the state of the blood run parallel, in a gen- 
eral way, but the degree of anaemia is a more delicate index of 
the patient's condition than even the temperature chart (Garrod). 

The Blood as a Wliole. 

Fibrin is greatly increased. In no other disease except in 
pneumonia is the network thicker or more rapid in formation. 
According to Maclagan, this is to be explained by an increase of 
tissue metamorphosis. Coagulation, on the other hand, is not 
quicker but slower than usual. 

Lactic acid is present in excess, but cannot be clinically es- 
timated, nor is its excess peculiar to this disease. 

The alkalinity of the blood had been reported diminished, but 
the technique is not considered reliable by the best observers. 

Bed Cells. — Hay em ^ and Osier ' state that the poison of acute 
rheumatism is a powerful and rapid destroyer of red cells. In 
acute cases, according to Hay em, the red cells lose at least 
1,000,000 of their number and in cases which drag along and re- 
lapse the loss is from 1,500,000 to 2,000,000. When an attack 
is cut short by salicylate treatment the drain on the corpuscles 
is stopped. 

So far as can be judged from the figures in Table XIII. of 
the Masachusetts Hospital cases this diminution does not seem 
to occur in all cases. Many of these cases had been sick some 
weeks before the time when the count was made, yet 'the counts 
are not very low. In the eight cases which have been sick over 
twenty days, the average of red cells is 4,462,000; in those sick 
between one and twenty days, 4,540,000 ; and in the whole group 
of cases, 4,400,000. The lowest count was 3,608,000. Accord- 
ing to Haj^em 4,000,000 is the usual count in acute cases and 
3,000,000 to 3,500,000 in those which drag on and relapse. 

Qualitative Changes. — Maragliano's so-called degenerative 
changes in the red cells have been observed in this disease, but 
are not very marked. Deformities and nucleated corpuscles 
appear only when the anaemia is very marked. 

Hcemoglohin. — As in all secondary anaemias the corpuscles 
get thin and pale before they die, and hence the coloring matter 
1 Loc. Git. , p. 917. 2 « Practice of Medicine, " 1895. 



182 



SPECIAL PATHOLOGY OF THE BLOOD. 



is diminished more than the count. The average haemoglobin 
percentage in this series is sixty -seven, and the color index .76. 
Hayem noted that, in some cases during convalescence, as the 
red corpuscles slowly increase the color index remains low or 
even goes lower still. 

Leucocytes. — All observers agree that leucocytosis is the rule 
and that its degree is roughly parallel to the acuteness and 
severity of the attack (the individual's vigor of reaction is al- 
ways a factor) and the amount of fever. The following tables 
illustrate the variations of the leucocytes in a fairly t^^pical way : 



Table XIII., A.— Acute Articular Rheumatism. 



6 


Age. 


Sex. 1 


Duration. 


Degree of 
inflammation. 


Red ceils. 


White 
cells. 


Per cent 
haemo- 
globin. 


1 

Remarks. 


— 
1 


50 


F 


17 days. 


Red and hot. 


"? 


39,000 


65 




2 


21 


TVT 
l>i . 


5 weeks. 


? 


4,160,000 


3 1, 500 


65 


Knees and 1 ankle. 


3 


59 


17" 

r . 


? 




5,476,0i)0 


27,000 


94 


Patient pale. 


4 


Adult. 


M . 


? 


? 




25,900 


• 


5 


33 


M. 


2 weeks. 


Red and hot. 


4,852,000 


24,500 


76 




6 


20 


F. 


9 


? 




22,400 




Acute endocarditis 
















also. 


7 


Adult. 


iU . 


? 


9 


4,216.000 


21,000 


56 




8 


23 


AT 


4 weeks. 


Tender and hot. 


5,192,000 


18,300 


70 


Temperature 102°. 


9 


28 


M. 


3 


9 




17.800 


9 


Many joints affected. 


10 


19 


M. 


4 days. 


Red and hot. 


9 


17,400 


? 


11 


49 


M. 


9 


9 


4,800,000 


17,700 


? 


Paronychia also. 


12 


49 


M. 


? 


'i 




17,100 


? 


Dec. 2d. 


13 


21 


F. 




Red and hot. 


3,944,000 


17.000 


45 


Cheeks rosy. 


14 


24 


M. 


2 days. 


? 


4,600,000 


16,000 


68 


15 


24 


M. 


? 


9 


4,670,000 


15.500 


68 




16 


35 


M. 








15,200 


45 




17 


13 


F. 


1 day. 


Red and hot. 


4,8i^6,000 


15.200 


65 


Temperature 102'. 




12 


M. 






4, 400 000 


15,000 


56 


19 


19 


M. 


4 days. 




4', 760,000 


14!.500 


75 


Severe case. 


20 


9 


F. 


? 




4.240,000 


14,386 


60 




21 


9 


F. 




Red and hot. 


9 


14,050 


? 




22 


47 


M. 


1 day. 




4,750',000 


14,000 


72 


One joint only af- 
fected. 


23 


25 


F. 


3 days. 


Tender and hot. 


4.850,000 


14,000 


75 




24 


18 


F. 


2 months 


No redness or 
heat. 


4,156,000 


14,000 


54 




25 


19 


M. 


9 


? 


4,172,000 


14,000 


70 




26 


19 


M. 


? 


9 


4,580,000 


13.500 


64 


Nov. 10th, 1895. 


27 


21 


F. 


1 day. 


Red and hot. 


9 


13,500 


9 




28 


29 


M. 


9 


9 


4,320^000 


12,750 


68 




29 




9 




? 


4,128,000 


12,650 


65 


Dec. 1st, 1895. 


30 


37 


F. 


1 mouth. 


Swollen, tender. 


5,320,000 


12,500 


64 




31 


2S 


M. 


? 




5,000,000 


12.500 


65 




32 


32 




? 


? 


9 


12,100 


? 


Purpura also. 


33 


30 


F. 


? 


? 


4,160'.0 0 


12000 






34 


47 


M. 


4 weeks. 


Very slight. 
Not " 


4,288,000 


12.000 


65 




35 


27 


F. 


3 days. 


3,880.000 


11,600 


65 




36 


17 


M. 


1 week. 




4,600,000 


11,500 


70 


Mild case. 


37 


27 


M. 


10 days. 


Hot and red. 


4,200,000 


11.500 


60 




38 


33 


M. 


4 weeks. 


? 


5,480,000 


11,000 


80 


Hands alone i n - 














volved. 


39 


18 


M. 




Not red and hot. 




10.000 




One joint only af- 














fected. 


40 


28 


M. 


3 weeks. 




3,608,000 


7,000 


40 




41 


Adult. 


M. 


? 


9 


3,768.000 


6,800 






42 


29 


M. 


9 weeks. 


Some joints hot. 


4,104,000 


5.500 


■ 58 


Fourth relapse. 


43 


30 


F. 


? 


? 


3,440,000 


4.700 


26 


Specific gravity 
1040. 










Average = 


4,400,000+ 


1 6.800+ 


67 





ACUTE ARTICULAR RHEUMATISM. 183 



Table XIII., B.— Subacute Articular Rheumatism. 



No 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 




1 


25 


M. 


4,750,000 


15,000 


60 




2 


30 


F. 


4,644.000 


13,000 


63 




3 


28 


F. 




10,600 


? 




4 


28 


F. 


4,684,000 


8,000 


75 




5 


Adult. 


M. 


4,016,000 


6,200 


41 




6 




F. 


4,188,000 


5,750 


73 






Ave 


rage = 


4,400,000 


9,760 


62 





Table XIII., C— Chronic Rheumatism, Chiefly Articular. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 




1 


78 


F. 




7,200 


9 




2 


19 


F. 


5,248,000 


8,300 


45 




3 


32 


F. 




6.400 


■? 




4 


58 


M. 


4,744,000 


6.500 


60 




5 


30 


F. 




6,100 


? 




6 


20 


m. 


5,576,000 


9,800 


62 










Average = 


7,400 







Table XIII., D.— Muscular Rheumatism. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


1 


46 


m. 


4,580,000 


7,500 


70 




2 


54 


m. 


4,360,000 


7,500 


75 




3 


38 


M. 


? 


6,600 


9 




4 


54 


m. 


3,820,000 


14,000 


58 


During febrile attacks. 


5 


27 


F. 


? 


6,000 


? 


Lumbago. 


6 


35 


M. 


? 


5,700 










Average = 


7,5004- 







The average leucocytosis in the acute cases is 16,800 ; in those 
mild and more chronic, so-called ''subacute'' cases the leuco- 
cytes range lower, averaging 9,760; while in chronic rheuma- 
tism, whether articular or muscular (including lumbago), there 
is no increase at all (average =7,450). 



184 



SPECIAL PATHOLOGY OF THE BLOOD. 



Summary. 

Anaemia with leucocytosis, tlie degree of which is a measure 
of the severity of the infection. Fibrin much increased. 

Diagnostic Value. 

The blood tells us little if anything that could not be learned 
in other ways. It does not differ at all from that of a septic 
arthritis, or from that of acute gonorrhoeal arthritis. 

The only cases that I remember in which a blood examina- 
tion has been valuable are the following : 

Case I. — The patient had musculai- pains, fever, and a his- 
tory of a malarial attack some months earlier. The question 
to be decided by the blood examination was between malaria 
and " rheumatism." The leucocytes were 23,600 per cubic milli- 
metre, which made it clear that the case was neither malaria 
nor "rheumatism," since the former never increases the leuco- 
cytes and the latter could only give so high a count in case 
genuine articular inflammation were present. The case turned 
out to be croupous pneumonia which the high leucocyte count 
strongly suggested. 

Case II. — Patient presented symptoms and signs of acute 
^polyarticular rheumatism with fever. The fever came down 
under salicylates, but soon rose again, and the man became 
wildly delirious. His delirium persisted after the salicylate 
was stopped. Several joints continued swollen and tender. The 
fever was very moderate, ranging between 99° and 101°. There 
were no rose spots and no spleen. The question arose as to 
whether it was a case of sepsis with localization in the joints, or 
whether it was a case of typhoid supervening on an arthritis of 
some kind. The blood count, w^hich was repeated several times, 
always showed a perfectly normal blood except for a slight an- 
aemia. The subsequent course of the case, during which he re- 
mained for nearly three weeks more or less delirious, made it 
clear to Dr. F. C. Shattuck, under whose care the patient was, 
that the diagnosis was typhoid. 

Chronic rheumatism (muscular or articular) produces no 
constant blood changes appreciable by clinical methods (see 
Table XIII., C and D). 

ASIATIC CHOLERA. 

In no other disease so far as I am aware has an acid 
reaction in the blood been reported. This is at the end of 



ERYSIPELAS. 



185 



life. All observers agree that the alkalinity is at least greatly 
reduced. 

Our knowledge of the corpuscles is best summed up in 
Biernacki's ' study of thirty-eight cases. 

Red Cells. — In the stadium algidum, or stage of collapse, most 
of the symptoms are due to the great concentration of the blood 
from the loss of serous fluid in the stools. Hay em found the 
increase of red cells from this concentration to amount to from 
1,000,000 to 1,500,000 per cubic millimetre. 

Biernacki ' found 7,662,500 in one case twenty -four hours 
after the beginning of the disease. The specific gravity may be 
as high as 1071 or 1072. 

White Cells. — Leucocytosis is present, not merely as the 
result of concentration, but as a genuine increase to at least 
double the normal count. Biernacki found that cases with par- 
ticularly high counts (40,000 to 60,000) were soon fatal, so that 
he considers a marked leucocytosis in the algid stage as a bad 
prognostic sign, although patients also die with low leucocyte 
counts in this period. Such a leucocytosis does not occur in 
ordinary diarrhoea or dysentery. 

Leucocytosis is present as early as twelve hours from the 
first symptom and lasts at least as late as the sixth day. In the 
stage of reaction it usually decreases. In one very mild case 
reported by Biernacki there was not only no increase, but leu- 
copenia (4,375 per cubic millimetre). 

The differential count shows from eighty -two to ninety-five 
per cent of adult cells and a corresponding diminution of the 
young forms. 

ERYSIPELAS. 

Halla, Pee, Eeinert, Rieder, and v. Limbeck agree that leu- 
cocytosis is usually present in well-marked cases. Yon Lim- 
beck finds the leucocyte curve" to run roughly parallel with 
the temperature chart, sometimes beginning to fall a little before 
the latter. The counts rarely run very high, yet Eeinert 
counted 39,627 in one case. Pee noted that the leucocyte count 
increases only while the process is spreading and that the size 



13 



^Deut. med. Woch., 1895, No. 48. 



186 



SPECIAL PATHOLOGY OF THE BLOOD. 



of the count was a tolerably accurate measure of the severity of 
the case. 

Rieder found in seven cases an average of only 15,000 per 
cubic millimetre despite very high temperatures. In one case 
the leucocyte count remained high after the temperature had 
fallen, but in the others it anticipated the temperature. In one 
mild case he found no leucocytosis. Adult cells are greatly in- 
creased as in other forms of leucocytosis. Hay em noticed the 
same dependence of the leucocyte count upon the severity of the 
process. 

In five cases at the Massachusetts General Hospital I found 
17,000, 14,000, 12,700, 7,250, and 6,200, the last tWo very mild 
<3ases. The count of leucocytes seemed proportional to the 
severity of the affection. 

When the disease occurred in "scrofulous" cases, Hayem 
found only 7,000-8,000 leucocytes per cubic millimetre, while 
in cases with very extensive process and high fever 12,000-20,000 
were present. He found also a loss of 500,000-1,000,000 in the 
count of the red cells, according to the severity of the case. 
This showed itself particularly just before the fall of the tempera- 
ture. I have seen no reference by other writers to the condition 
of the red cells in this affection. 

TONSILLITIS (FOLLICULAR). 

Halla,' Pick,' and Pee^ found leucocytosis as a rule in un- 
complicated follicular tonsillitis; Rieder found it in a case 
complicated with acute nephritis. 

The following table confirms these observations in the main, 
though in mild cases no leucocytosis was present. 

The blood examination has no diagnostic value so far as I 
am aware. It is worth knowing that a simple tonsillitis can 
oause leucocytosis, to the end that if such is discovered on blood 
examination we need not suppose that some other process is 
present to account for the increase. 

1 Zeitschrift f . Heilkunde, 1883, p. 198. 

2 Prag. med. Woch., 1890, p. 303. 

3 Pee : Inaug. Dissert. , Berlin, 1890, p. 8. 



GRIPPE. 



187 



Table XIV. — Tonsillitis. 













Per cent 




d 


Age. 




Red cells. 


^ liite cells. 


tl 861110- 


Remarks. 










globin. 




1 


30 


F. 


4,750,000 


16, 000 


80 


Temperature 101 ^ 


2 


27 


M. 


4,556.000 


15,500 


67 


Six days ; slight. 


3 


Adult. 


F. 


4, 860,000 


14,000 




Follicular. 


4 


30 


M. 


4,730,000 


13,500 


76 


Convalescent. 


5 


24 


F. 


5,000,000 


13,500 


68 


Follicular. 


6 


Adult. 


M 




13,500 
12,250 






7 


M. 


4,952,000 


94 




8 


24 


F. 


5,816,000 


11,900 


65 


Streptococcus ; slight articu- 
lar rheumatism. 


.9 




M. 


5,000,000 


11,800 


90 


Follicular. 


10 


i9 


F. 


4,552,000 


11,600 


52 




11 


18 


M. 


5,150,000 


11,500 


83 


Chronic recurrent ; out in 














two days. 


12 


22 


F. 


5.016,000 


9,600 




13 


Adult. 


F. 


4, 200, 000 


5,800 


60 


Follicular. 


14 


23 


F 




7, 925 


52 


Follicular ; slight ; tempera- 
ture 99" next day. 







GRIPPE. 

The references in literature to the blood of grippe are very 
scanty. Orion (ArcJiiv. d. Med. milit., 1890, p. 280) found 
fibrin increased during the early days of the disease. Eieder 
Qluncli. med. WocJi., 1892, XXXIX.) found no leucocytosis in 
grippe and but little in the "catarrhal pneumonia" foUoT^dng 
it. 

In the following table it is evident that the red cells are not 
perceptibly affected and that the leucocytes remain normal in 
at least three-quarters of the cases. Only seven of the thirty 
cases showed leucocytosis, and in one or more of these some 
complication was very possibly present. This is of impor- 
tance in excluding pneumonia and local inflammatory condi- 
tions. The blood does not help us to distinguish the disease 
from typlioid. From malaria it may be distinguished by the ab- 
sence of malarial organisms. In one case (No. 30, Table XY.) 
after an operation for traumatic epilepsy, the temperature rose 
to 104°, with a chill, and the question of meningitis was consid- 
ered. The absence of leucocytosis excluded the meningitis and 
the attack turned out to be grippe, which was just then very 
prevalent. 



188 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XV. — Grippe. 



d 


Age. 


<D 


Kea ceils. 


White cells. 


Per cent 
haemo- 
globin 


Kemarks. 


1 


37 


M 




14, 200 




13th, coarse rales in both 








chests ; chlorides dimin- 














ished. 










9,200 




15th. 


2 


Adult. 


M. 


4,840,000 


14,400 




And bronchitis. 


3 


35 


M. 


5,111,200 


12,800 


97 


Pharyngitis ; cough ; consid- 














erable sputa ; constipated. 


4 


36 


F. 


4,771,700 


12,100 




With pharyngitis. 


5 


Adult. 


F. 




12 000 


62 


6 


32 


F. 


3,850,000 


11^500 


85 




7 


27 


F. 




11 1 00 






8 


50 


F. 




10,900 




Fine rales and increased 














voice sounds. 


9 


19 


F. 


5, 720, 000 


10.400 




11th, hysteria (?) ; tempera- 














ture, 105°. 








5,192,000 


7,600 


57 


27th, 30th, chill; cyanosis; 














weak rapid pulse ; 82 per 














cent of adult cells; autopsy. 


10 


19 


M 




10,300 




11 


Adult. 


M. 


4, 950, 000 


10,000 






12 


35 


M 


9,900 






13 


40 


M. 


5, 904, 000 


9,400 




Subacute laryngitis. 


14 




F. 


4 8fi0 000 


9 200 




15 


Adult. 


F. 


4, 900, 000 


9^000 






16 


31 


M. 


5,310,000 


9,000 






17 


32 


F. 


4,200.000 


8,000 


25 




18 


23 


M. 


5,500,000 


7,400 






19 


25 


M. 


5,616, 000 


6,800 






20 


Adult. 


M. 


4. 040 000 


6,800 




VV lull vlXJ' LIltjLiX 1C5^V . 


21 


42 ' 


m! 


5,856.000 


6,000 




22 


24 


M. 


4, 952,000 


6,000 






23 


Adult. 


M. 


4,559,000 


5,600 






24 


30 


M 


5, 500 






25 


Adult. 


M. 


5, 600, 000 


4,600 






26 


44 


M. 


5,685,000 


4,550 






27 


31 


M. 


5.424,000 


4,000 






28 


Adult. 


M. 


5.260,000 


3,500 






29 


30 


F. 


5,488,000 


3,144 






30 








2.600 




Temperature 104° ; ten days 










after a head operation ; 














question of meningitis. 



SEPTICEMIA. 

Puerperal septicaemia, infected wounds, septic arthritis, 
septic endocarditis, general infections with pyogenic bacteria, 
"pyaemia," are all identical so far as their effects on the blood 
are concerned, and will be considered together under the general 
head of Septicfemia. 



SEPTICEMIA. 



189 



Bacteriology of the Blood. 

Cocci can be demonstrated in cultures from the blood of sep- 
ticaemia more frequently than in any other class of infections. 
Rosenbach ^ in 1884 found streptococci and staphylococci in 
sepsis. Garre ^ in 1885 found the last-named coccus in a case of 
osteomyelitis. In 1890 v. Eiselsberg ^ found staphylococci in 
ten cases of septic wounds and one case of osteomyelitis, and 
streptococci and staphylococci together in five more cases whose 
wounds had become septic. 

Czerniewsky/ Stern and Hirschler^ found the same organ- 
isms in puerperal fever, the former observer in five cases. 

Brunner,' Hofi"," and Blum' found pyogenic staphylococci 
in pyaemia and sepsis, and Saenger,^ Eoux and Lannois,'" 
Cantu,'' and Bommers had equal success, each in a single case. 

Canon and Sittmann investigated large numbers of cases 
with many positive results, and Grawitz ^'^ and Petruschky were 
successful in finding pyogenic cocci in the blood of cases of 
ulcerative endocarditis as well as in other septic infections. 

Taking the results of all these investigators together, it seems 
evident that in the majority of cases of septicsemia, blood cul- 
tures, taken according to the directions on page 35, show the 
presence of pyogenic organisms, and that in many obscure septic 
cases the diagnosis may be greatly facilitated by such an exam- 
ination. Negative results are of course very far from excluding 

' "Microorganismen b. d. Wundinfectionskrankheiten, " etc., Wies- 
baden, 1884. 

2 Fortscb. d. Med., 1885, No. 6. 
3Wien. klin. Woch., 1890, No. 30. 

4 Arcbiv f. Gynakol., 1888, No. 33. 

5 Wien. med. Presse, 1888, No. 28. 
eWien. klin. Woch., 1891, No. 20. 
' Dissert. , Strassburg, 1890. 
^Miinch. med. Woch., 1893, No. 16. 
9 Deut. med. Woch., 1889, No. 8. 

^0 Revue de Med., 1890, No. 12. 
^' Rif. Med., 1892, No. 96. 
12 Deut. med. Woch., 1893, No. 16. 
'3 Deut. Zeit. f. Chirurg., 1893, p. 571. 
14 Deut. Arch. f. klin. Med., 1894, p. 573. 
^5 Charite-Annalen, 1894, vol. 19. 
Zeit. f. Hygiene, 1894, pp. 59 and 413. 



190 



SPECIAL PATHOLOGY OF THE BLOOD. 



septicaemia, but positive ones are sometimes of great value if 
proper precautions are taken in the technique of the examina- 
tion. In the diagnosis of malignant endocarditis, often a most 
difficult one, Grawitz thinks blood cultures are especially im- 
portant and likely to prove positive when the disease is present 
(see Diseases of the Heart, page 255) . 

Red Cells. — All observers agree that very marked anaemia is 
present in severe cases. Roscher's' investigations tend to show 
that the diminution in red cells in septicaemia is greater than in 
any other infective disease, and appears in a shorter time. He 
found such a diminution present no longer than a few hours from 
the beginning of the illness. He finds the amount of anaemia 
proportional to the severity of the case, and (reckoning by means 
of the estimated solid residue) conclude^ that whenever the blood 
has lost one-quarter of its substance or more, death follows. 
He considers, therefore, that help as to prognosis is given us by 
the blood examination in septicaemia. 

The serum becomes very watery, partaking of the general 
atrophy of the blood tissue. In a case of intensely acute puer- 
peral sepsis Grawitz found the red cells reduced to 300,000 (!) 
although the patient had been sick less than twenty-four 
hours. The case seems almost incredible, but is reported in 
great detail in the author's recent text-book, to which reference 
has so frequently been made. He accounts for it by the combi- 
nation of blood destruction and dilution. 

In the nine cases of puerperal sepsis seen at the Massa- 
chusetts General Hospital in recent j^ears the red cells averaged 
3,780,000, which is very low, considering the shortness of the 
illness in most cases. (The influence of hemorrhage during 
parturition must of course be taken into account.) 

In most of the septic wounds which I have seen the counts 
have not been low. But in one case of septicaemia from a sup- 
purating fibroid of the uterus the red cells numbered only 
1,800,000. 

The licemoglobin is usually diminished about as much as the 
corpuscles. According to Bond it tends to crystallize about the 
edge of a slide and cover-glass preparation of the fresh blood. 

Deformiths in the shape and size of the corpuscles are not 
usually present except in the severest cases. 

' Inaug. Dissert., Berlin, 1894. 



SEPTICAEMIA. 



191 



Table XVI. — Puerperal Septicemia, 













Per cent 




d 


Age. 


Red cells. 


White cells. 


haemo- 


Remarks. 




m 






globin. 




1 


21 


F. 


2,300,000 


26,000 






2 


29 


F. 


3,900,000 


23, 900 
21,000 
9, 500 
15,500 

15,000 
11,800 


68 


Two days before delivery. 

Day of delivery. 

One day after delivery. 

Five days after delivery ; 
breasts caked. 

Ten days after delivery. 

Twenty-six days after de- 
livery. 


3 


28 


F. 


3,784,000 


22,000 
13,600 

8,300 
15, 800 
14,900 
15,000 

9,500 


55 


Miscarriage five days before ; 
septic ; curetted. 

Tliree daj^s later, tempera- 
ture falling. 

Seven days later, tempera- 
ture normal. 

Fourteen days later, tempera- 
ture up ; curetted again. 

Fifteen days later, tempera- 
ture falling. 

Sixteen days later, tempera- 
ture falling. 

T'V*! -t;wr> flpvcs laf^PT t;PT>T - 

perature falling. 


4 


25 


F. 


2,936,000 


20,000 
21,000 




April 1st, 1894. 
" 3d, 1894. 


5 


32 


F. 


4,904,000 


19, 300 




Curetted. 








9,300 




One week later, well. 


6 


24 


F. 


3,556,000 


18,400 






7 




F. 


Marked 




Adult cells, 94^ ; young cells, 








increase. 




8 


19 


F. 




9,000 
5,600 




Curetted the day before. 
Died. 


9 


26 


F. 


5,368,000 





Hcemoglobinoemia with reddisli staining of the serum is often 
noticeable in the dried and stained cover-glass specimen where 
the plasma is deeply stained. 

Leucocytes, — Considerable controversy has taken place as to 
the changes in the white cells effected by septicaemia; some ob- 
servers finding leucocytosis, while others find none. 

The results of experimental infections referred to above (see 
page 95) and the parallelism of the leucocyte changes in pneu- 
monia, peritonitis, and diphtheria fully explain these appar- 
ent divergences, which perfectly exemplify the rules stated on 
page 91. 

Leucocytosis occurs only when the struggle between the pa- 
tient and his disease is intense, and whichever is victorious. 



192 



SPECIAL PATHOLOGY OF THE BLOOD. 



When either side wins without any difficulty, i.e., in the mildest 
and in the severest cases, leucocytosis is nearly or entirely ab- 
sent ; indeed, leucopenia may be found (as for instance in a case 
of septic endometritis reported by v. Limbeck — only 3,000 leu- 
cocytes). Yon Limbeck and Ej:ebs ' found no leucocytosis in 
cases of perpetual septicaemia, but these were all fatal cases or 
yery mild ones. Rieder, on the other hand, and the great major- 
ity of other observers (Sadler,^ Roscher,^ Kanthak,"* Grawitz, 
etc.) find leucocytosis. This means that in most cases ob- 
served by these writers the infection was of moderate severity. 

Only two of the twenty-one cases in Tables XVI. and XYII. 
showed no leucocytosis. One was very mild, the other died on 
the day of the count. 



Table XVII., A. — Septic Wounds. 



d 


Age. 


<D 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


37 


F. 


5,880,000 


48,400 




Sloughing breast ; bedsore. 


2 


28 


M. 


7,600,000 


25,400 




Septic wound of foot. 


S 


31 


F. 


5,680,000 


15,300 




Sloughing breast after cancer 










6, 700 




operation. 








5,840.000 


23,200 




One month later ; wound clean. 


4 


27 


M. 


4,450,000 


10,500 




Septic hand. 


5 




M. 


5,600,000 


8,800 




Septic finger. 



Table XVII., B.— Septicemia w^th Arthritis. 



d 


Age. 


>i 

V 


Red cells. 


White 
cells. 


Per cent 
hgemo- 
globin. 


Remarks. 


1 


8 


M 


25,000 
43,000 




Pus in elbow joint ; no injury. 
Two daj^s after operation, vent 

not free ; opened further. 
Seven days after operation. 
Eight days after operation. 
vSixteen days after, well. 
Gonorrhoeal, pus in knee. 
Pus in shoulder joint, no trauma, 
Gonorrhoeal ankle. 




















24, 000 
20, 700 
6,700 
























2 
3 


34 
59 


M. 

M 


4,520,000 


19,000 
18,500 
13,800 


65 


4 


22 


M 






5 


39 


M 




8,940 




Gonorrhoeal ankle ; cultures neg- 
ative. 









1 Krebs : Dissert. , Berlin, 1893. 

2 Sadler : Loc. cit. 

3Roscher: Dissert., Berlin, 1894. 
Kanthak : Brit. Med. Journal, June, 1892. 



SEPTICEMIA. 



193 



Table XVII., C— General Streptococcus Septicemia. 



d 


Age. 


XJl 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 


Adult. 


M. 
F. 


5,248,000 
1,800,000 


41,400 
46,000 




Suppurating fibroid. 









Summary. 

1. Rapid development of severe anaemia. 

2. Leucocytosis marked, except in very mild or very severe 
cases. 

3. Blood cultures often contain pj'ogenic cocci. 

Diagnostic Value. 

The advantage of a positive bacteriological examination is 
obvious. Of the value of the blood count in distinguishing septic 
from non-septic wounds and estimating the degree of sepsis and 
the importance or needlessness of operative interference, not 
much is known. The subject deserves to be carefully worked 
out from a surgical point of view. The following cases, how- 
ever, tend to show that we might utilize blood counting far more 
than we do to determine questions of this sort : 

Case I. — Frank B was a case of appendicitis operated on 

by Dr. M. H. Eichardson at the end of an attack. A little pus 
was found, the appendix was excised, and the wound nearly 
closed, a small strand of gauze, however, being left in. Several 
days after the operation, there being at the time no external dis- 
charge, the temperature rose. The wound seemed perfectly 
clean. The man was very nervous about himself, and much 
stirred up at each dressing ; and as the temperature never went 
higher than 101°, there seemed to be considerable doubt as to 
what the cause of the temperature was. The blood count in 
this case showed 52,000 leucocytes. On opening the wound a 
large amount of broken-down blood clot was evacuated, and the 
temperature came down to normal. 

Case II. — Mrs. S — ■ — was a case of pus tube shelled out and 
sewed up tight. Ten days after the operation the temperature 
began to look as if pus were present. Here again the patient 



194 



SPECIAL PATHOLOGY OF THE BLOOD. 



was exceedingly nervous ; and, as so often liapx3ens, the question 
was asked and re-asked, whether she was keeping up her own 
temperature by the state of her mind. The blood count, how- 
ever, showed marked leucocytosis, which led to a careful ether 
examination, revealing a fluctuating mass behind the uterus, 
from which pus was obtained by puncture. 

Case III. — Mr. R entered the Massachusetts General 

Hospital in December, under the service of Dr. C. B. Porter, 
with a compound fracture of the thigh. Some days after it had 
been put up, the temj)erature began to suggest the presence of 
pus, the wound, however, remaining perfectly clean. I counted 
the blood, and found a marked leucocytosis. A more thorough 
exploration of the wound revealed a pocket of pus, the evacu- 
ation of which brought down the temperature. I was not sure 
in this case whether the absorption of the blood clot, such as 
takes place, I suppose, after any compound fracture, would be 
sufficient to cause leucocytosis. I therefore counted several 
cases in which there was fever and presumably blood-clot ab- 
sorption, namely, a hsemothorax, a pelvic haematocele, two com- 
pound fractures, and a crushed foot ; in none of these was any 
leucocytosis present. 

Case rV^. — Mr. S was operated on by Dr. J. C. Warren for 

traumatic epilepsy. Nothing special was found, and the wound 
was closed. Ten days after the operation the temperature rose 
to 104°, and the patient complained of severe headache and pain 
in the back. I counted the blood, and found no leucocytosis. 
Next day the temperature was down. The patient apparently 
had the grippe. 

Several cases in which an old malaria was supposed to be 
" brought out" by a surgical operation, the patient having irreg- 
ular fever and chills after the operation, have sho\\Ti, on exam- 
ination of the blood by the writer, no malarial organisms but 
marked leucocytosis. In these cases the symptoms of " majaria" 
ceased when the wound was more thoroughly drained, and I 
have no doubt that many cases of "malaria" after surgical oper- 
ations are really wound sepsis. 

It is difficult to make inferences from a leucocytosis in such 
cases, because no one, so far as I know, has thoroughly investi- 
gated the blood condition during the normal healing process of 
wounds. But there are certainly many cases in which we need 
the kind of information about the condition of a wound which 
the blood might give us, if the changes in connection with 
wounds were better known. 



APPENDICITIS. 



195 



How often the questions are asked : Is this patient septic? 
Does this temperature mean anything of importance? Is this 
wound well drained? Is this complaint of pain hysterical or 
does it mean something operable? 

How often the blood count would help us to answer such 
questions without leaving it for time to settle them after the 
most urgent need of settling them is gone, we do not yet 
know. 

In puerperal cases, the fact that leucocytosis is always 
present for several days after delivery makes it harder to judge 
from the blood whether a given case is septic. I doubt if the 
blood count will give any information on this point not to be 
more easily obtained in other ways. Blood cultures, if positive, 
are of far greater importance, but take more time. 

ABSCESS. 

The effects of abscess upon the blood are, I suppose, due to 
septicaemia. Nevertheless septicaemia loitli abscess formation 
differs enough from septicaemia ivithout abscess formation, both 
clinically and haematologically, to make a separate description 
convenient. 

The most easily studied variety of abscess is that connected 
with appendicitis, inasmuch as the frequency of operations in 
such cases gives us opportunity to verify what we suppose to be 
indicated by the blood count and see how far our suppositions 
are true. 

At the Massachusetts General Hospital, most patients with 
other varieties of abscess go straight to the surgeon and their 
blood is not examined, but many cases of appendicitis come 
first to the medical wards, and hence we have records of over 
eighty cases whose blood has been examined. 

I shall therefore begin the description of the blood in abscess 
by an account of appendicitis, which may probably be considered 
a typical case of abscess formation. 

APPENDICITIS. 

After excluding all cases in which the diagnosis was not sure 
we have left seventy-two cases. 



196 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table XVIII.— Appendicitis. 



10 



35 



19 31 M. 



3,400,000 
6,800,000 



5,184,000 
4,800,000 
4,890,000 
6,000,000 
6,500,000 
5,072,000 



5,200,000 
5,144,000 



52,000 
43,000 
39,900 
36.800 
36,000 
35,000 
34,000 
34,000 
28,000 
24,200 

16,850 
15,600 
10,700 
15,100 
14,600 
11,800 
17,850 
18,200 
13,100 

24,000 

12,500 
19,500 
24,000 
23,000 
16,100 
22,500 
13,000 

9,500 
22,300 

9,500 
22,000 
19,400 
14,900 
21,900 

21,700 
21,400 
16,000 
24,400 
20,200 
47,700 
16,700 
13,000 
10,700 
30,300 
20,900 
17,700 
25,100 
28,100 
20,400 
15,400 
25,000 
11,900 
15,600 
21,900 
19,000 
11,900 
12,800 
11,700 
12,300 
15,600 
18,400 
14,700 
16,500 
11,300 
20,540 




Hi 



82 



Remarks. 



Question of typhoid; pus found at operation. 
Chronic case; 96 per cent, of adult leucocytes. 



Three days after operation. 
Seven •' 

Second attack; operation at 11 p.m. November 5th, 

count at 5 : 30. 
Serous peritonitis found. November 6th, 5 p.m. 
November 7th, 3 p. M. 

8th, 4 " 

Temperature still up. November 9th, 5 p.m. 
November 10th, 5 : 30 p. m. 

11th, 8:30 " 

12th, 8:30 " 

13th, 8 a.m. 

13th, 8: 30 p.m. 
Recovery complete ten days later. 

24° September 1st; operation, free turbid fluid without 

adhesions. 
September 10th. 

" 12th ; pocket of pus found. 

January 14th. 

" 15th; before operation, 5 v. -{-pus. 
Not operated ; entrance. 
Second day. 
Third 

12: 20 operated; belly full of pus. 
8: 30 moribund; blood dark and hard to get. 
July 6th. 
" 8th. 

" 10th, 104°; recovery. 
Appendicitis eight to nine days; operation; post-csecal 



November 5th, first operation. 
10th. 



13tli. 
15th. 
16th. 
19th, 
20th. 
21st. 
22d. 



second operation (pus pocket). 



26th, third operation (pus pocket). 
27th. 
28th. 
29 th. 
30th. 

December 1st. 

2d. 

3d. 

4th. 

5th. 

6th. 

7th. 

8th. 

9th. 
10th. 
11th. 
12th. 
13th. 
21st. 
25th. 
26th 
October 5th. 



APPENDICITIS. 



197 



Table XVIII.— Appendicitis {Continued). 



31 



M. 



24 



20 



23 



4,800,000 
5,564,000 
4,670,000 
5,296,000 



4,680,000 
4,688,000 



5,120,000 
5,680,000 



6,160,000 



3,300.000 
4,380,000 



4,380,000 
5,910,000 



4.250.000 



4,950,000 
5,000,000 
4,626,000 



100 
000 
400 
,250 
750 
600 
000 
,000 
000 
000 
000 
,000 
000 
750 
000 
600 
000 
933 
500 
000 
930 
000 
500 
250 
450 
000 
20U 
200 
051 
000 
000 
500 
800 
000 
000 
000 
500 
600 
000 
600 
500 

900 
300 
800 
523 
330 
800 
,000 
700 

700 
150 
,400 
300 
000 
400 
200 
000 
000 
000 
000 



70 




Remarks. 



; not operated. 

liquids every two hours. 



pain and vomiting. 
100,6°^; discharged. 



October 6th. 
8th. 

" 9th ; moved bowels. 
12th ; tender still and tense. 
99° to 100° temperature. 
Normal; still sore. 

Appendicitis twentj^-four hours; resistant belly. 
October 23d. 

24th, 9 A. M. 

24th, 4 p. M. 

24th, 11 p. M 

25th, 8 a.m. 

25th, 3 p.m. 
May 24th. 

" 25th. 
June 5th ; temperature, 101.4 
June 7th ; no pain. 

" 8th ; no pain ; temperature. 
Operated; pus. 

January 13th. 

15th. 
29th. 
February 1st. 

" 5th; after operation. 
No operation. 
Purulent peritonitis. 



Accident case; operation; pint of pus under pressure. 
Fifth day. November 7th. 
November 8th. 

" 11th; not operated; well on 17th. 

Eighth day ; operation ; large abscess cavity. 

Operated. 

Entrance. 

Same evening; no operation. 
Next day. 

General peritonitis, 
November 12th, noon. 

12th, 8:30 p.m. 
" 13th, 8 A.M.; not operated. 

13th, 8 P.M. 

March 25th, 9 p.m. ; vomiting, pain, tenderness. 

" 27th ; comfortable, no vomiting; signs more 

locahzed. 
" 28th ; slight tenderness only. 
"• 5i9th ; bowels move well ; no symptoms. 
" 30th; operation; large amount of pus. 



20th 
21st ; 



general peritonitis. 



Five days ; third attack; operation; free turbid fluid, 

no perforation ; prompt recovery. 
27th, 8 P.M. 

28th ; symptoms less ; no operation. 
February 2.3d, I ^ J. ^ 

Catarrhal. 

3 P.M., November 9th; appendicitis twenty-four hours. 
5 P.M., November 10th; temperature, 98.8°. 



Visible tumor. 



March 27th. 

April 26th, operated; pus. 



198 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table XVIII. —Appendicitis {Continued). 



§ 2.9 



Remarks. 



4,860,000 



4,664,000 



3,690,000 
5,600,000 



5,106,000 
5,600,000 
6,500,000 
6,500,000 

6,000,000 



4,320,000 



12,000 

16,900 
11,900 

11,800 

19,900 

11,700 
17,600 
16,670 
11,950 
10,800 
10,875 
31,000 

10 700 
9,000 

10,500 
10,400 
9,800 
10,400 
10,500 
10,140 

10,040 
9,000 
8,400 

10,000 
7,200 
7,600 
7,760 
7,600 
7,600 
7,6C0 
7.050 
7,000 
6,600 
6,000 



58 



85 



Appendicitis cake. August 3d, operation; gangrenous 

appendix with adiiesions. 
August 6th, faecal fistula. 

No symptoms except pain for twenty-four hours; not 
operated. 

Very slight tenderness; no resistance or dulness. 
July 6th. 

Temperature up: tenderness and resistance. July 7th, 

operation; pus found. 
December 28th, 4 p.m. 

30th, 10 a.m. 
31st, 11 " 
January 1st, 9 p.m. 
5th. 

July 27th; nine days pain and vomiting. 

July 28th; more pain, tenderness and vomiting; opera- 
tion showed pus. 

November 7th, appendicitis six days. 

Operation; abscess with considerable pus; gangrenous 
perforated appendix with concretion in it. 

Not operated till later. 

February 6th. 12 m. ; slight pain and tenderness. 

" 7th, 3 p. M. ; temperature dropping. 
Catarrhal. 

One week, fourth attack; no cake, no acute symptoms; 

operation; no pus. 
Sixth day, operation; abscess, |i. pus. 
Operated: no pus: catarrhal. 
December 1st. 

6th. 
15th. 
16th. 

No pus. 

No operation. 
No pus. 

Catarrhal appendix; five days in hospital. 
Catarrhal appendix. 

" chronic; nearly well; operation; no pus. 

" or very slight. 



From the seventy -two cases of the adjoining table, the fol- 
lowing conclusions are to be drawn : 

1. Bed cells : no changes except in chronic cases with long- 
standing abscess. 

2. Coagulation often slow, but fibrin always increased in 
suppurating cases. 

3. As in most infections the mildest and the severest cases 
show no leucocytosis. Four cases loith general purulent peri- 
tonitis sJioived no leucocytosis, its absence being confirmed by 
repeated examinations. The total absence of leucocytosis in a 
case not obviously mild is a very bad prognostic sign as in pneu- 
monia and diphtheria. 



APPENDICITIS. 



199 



4. Catarrhal appendicitis is rarely accompanied by leucocy- 
tosis (only once in this series — 14,000). 

5. An increasing leucocytosis means a spreading process and 
may he the only evidence of the fact. In Case 40 of this series, 
the patient entered with vomiting, localized pain and tender- 
ness. The leucocytosis was 15,600. Three days later he was 
comfortable, had no vomiting and very little tenderness, and in 
all respects seemed to be improving, yet the white cells had 
risen to 22,900. Operation was postponed owing to the lack of 
all unfavorable symptoms except the blood count. Next day the 
bowels were moving well and the patient had no fever and no had 
symptoms of any kind, but his leucocytes had risen to 35,300. 
On the following morning the surgeon was finally persuaded to 
operate and found a large amount of pus. 

A steadily increasing leucocytosis is always a bad sign and 
should never be disregarded even when (as in this case) other 
bad symptoms are absent. It is of far more significance than 
a larger count which does not increase. 

6. The size of the leucocytosis is of comparatively little 
significance. A low count (8,000-11,000) means one of three 
things : 

(a) A mild case. 

(6) A very severe case. 

(c) An abscess thoroughly walled off. 

After the abscess has ceased to spread and has become well 
walled off, the leucocyte count remains stationary or decreases. 
If it bursts into the general peritoneal cavity the count may 
rise sharply or it may fall to normal or subnormal, its move- 
ment depending on the degree of resistance which the system 
offers. 

7. In the majority of cases the pus is neither completely 
walled off nor free in the belly, and such cases are accompanied 
by a moderate and fluctuating leucocytosis, which rises and falls 
according to a varietj' of conditions which cannot be accurately 
interpreted. 

It usually increases in the first three or four days of the ill- 
ness, and then becomes stationary or declines if the case is tak- 
ing a favorable course {i.e., if the pus is being absorbed or 
walled off) , while it continues to increase when the case is going 
on from bad to worse. 



200 



SPECIAL PATHOLOGY OF THE BLOOD. 



Case 20 illustrates the course of the leucocytes in a favorable 
case not operated on ; the leucocytes fell gradually but steadily 
from hour to hour so that in two days the count came down from 
20,100 to 8,750, the tumor and tenderness simultaneously dis- 
appeared, and the patient was well in a few days more. Case 38 
(iropped in eight hours from 16,000 to 8,000 and quickly recov- 
ered. In Case 19, the leucocytosis fell in three days from 33,000 
to 9,200, but rose again when the bowels were moved by enema, 
and took some days to reach normal again. Evidently the per- 
istalsis injured the abscess wall so that the process began to 
spread again and had to be walled off afresh. 

8. When a leucocytosis of 18,000-25,000 is maintained for a 
number of days it usually means a large abscess pretty well 
walled off. 

9. The majority of cases as seen at the Massachusetts Gen- 
eral Hospital on the second, third, and fourth day of the ill- 
ness show leucocytosis of 15,000-24,000, thirty -three of the 
present series falling within these figures. Counts larger than 
this have always been proved to mean a lar^e amount of x>us or 
a general peritonitis. Of the cases below 15,000 (fifteen in all) 
twelve did not come to operation, or if operated showed no pus. 
This statement excludes the four cases of general purulent peri- 
tonitis without leucocytosis mentioned above. 

10. Case 18 illustrates several points. After the first opera- 
tion the leucocyte count did not fall so rapidl}^ as usual, and the 
cause of this soon turned out to be a pus pocket, after the evac- 
uation of which the count fell in twenty-four hours from 47,700 
to 16,700, only to rise again for another accumulation of the 
same kind. 

After this last (third) operation the case progressed slowly 
but favorabl}^ and yet the leucocyte count remained more or less 
above normal for a month. The wound was healthy, freely dis- 
charging, and had healed satisfactorily at the time of the last 
count recorded. 

Whether all wounds follow this course as regards the leu- 
cocytes I do not know. It is an important point which needs 
working out, namely : What is the normal behavior of the blood 
count during the healing of granulating wounds? If this were 
known, we might get valuable information as to whether a 
wound is doing well or not, by means of the blood count, which, 



APPENDICITIS. 



201 



if septic, would probably behave differently from its wont in 
wounds wliicli do well. As it is, all these questions are not an- 
swerable. It is to be hoped that surgeons will investigate them. 

Differential Diagnosis. 

1. The presence of a marked leucocytosis excludes simple 
colic with or without constipation, and excludes certain forms of 
intestinal obstruction (if uncomplicated). Such cases of intes- 
tinal obstruction as are complicated with ulceration or gangrene 
or due to cancer may raise the leucocyte count. 

Between general peritonitis from an appendicitis and intes- 
tinal obstruction, the presence of marked leucocytosis points to 
the former; but its absence may accompany either affection. I 
remember a case in which the diagnosis lay between these two 
affections, and operation was delayed because the absence of any 
leucocytosis was thought to rule out peritonitis, and it was 
hoped to get the bowels started by enemata, etc. When finally 
the abdomen was opened stinking pus gushed out and the 
patient died the same day. 

2. Treves ' has reported several cases in which it was hard 
to decide whether the diagnosis was typhoid or appendicitis. 
A blood examination would probably have decided the matter as 
it has in three cases in the writer's experience. Most cases of 
appendicitis of any severity show leucocj^tosis; typhoid almost 
never does if uncomplicated. Curtis ^ reports a case of typhoid 
with a tumor and tenderness in the right iliac region which 
closely simulated appendicitis but turned out to be a floating 
kidney. The blood count would have decided the matter. 

3. Between appendicitis and pus tube the blood gives no 
help, as both affect it alike. 

4. Ovarian or pelvic neuralgia (uncomplicated) never causes 
leucocytosis and may be excluded hj its presence. The same 
is true of floating kidney, which has been sometimes con- 
founded with appendicitis. 

5. Gall-stone colic, and renal colic if uncomplicated by 
inflammatory disturbance, cause no leucocytosis, and can 
•therefore be distinguished from appendicitis in most cases. 

* Medico-Chirurgical Transactions, 1888, Ixxi. , p. 165. 
2 "Twentieth Century Practice of Medicine," vol. viii,, p. 461. 
14 



202 



SPECIAL PATHOLOGY OF THE BLOOD. 



If cholangitis, cholecystitis, pyelitis, or severe cystitis com- 
plicate the colic, the examination of the blood will be no help 
to us. 

6. Impaction of fceces in the caecum will not cause any leucocy- 
iosis and may be excluded when such is present. The count 
may be of use, it seems to me, in deciding us whether an enema 
ought to be given. It is sometimes desirable to give an enema 
in cases simulating appendicitis, to help clear up the diagnosis, 
but some physicians are afraid to do so for fear of causing a 
walled-off abscess to break into the general peritoneal cavity. 
In such cases, if no leucocytosis were present, we might go 
ahead with a clearer conscience. 

Mr. B entered the Massachusetts General Hospital Sep- 
tember 20th, 1893, with a diagnosis of appendicitis. For twenty 
days he had been having pain and tenderness in the region of 
the appendix, pain being controlled by morphine. The bowels 
had been loose, he said. There was dulness, tenderness, and a 
distinct tumor in the region of the appendix, with slight pyrexia. 
The blood count showed only 8,000 leucocytes. He was given 
a compound cathartic pill, had a large movement of the bowels, 
and all symptoms and signs disappeared. 

7. Extra-uterine pregnancy and pelvic haematocele may cause 
leucocytosis like appendicitis, but do not increase fibrin unless 
peritonitis is present, and are likely to sTiow a marked diminution 
in red corpuscles if the hemorrhage is severe. The red cells 
are normal in appendicitis except in chronic cases with ab- 
scess. 

8. Floating kidney has been already mentioned in Curtis' case, 
where in combination with typhoid it closely resembled appen- 
dicitis. Even without the presence of typhoid, the same dif- 
iiculty of diagnosis may arise between appendix and floating 
kidney. The presence of leucocytosis could not be accounted 
for by the latter. 

One of the next most common forms of abscess seen in 
medical wards is pyosalpinx, which I shall call by the English 
name of "pus tube." As this produces the same effect on the 
Mood as pelvic abscess or pelvic peritonitis, I shall consider the 
three processes together. 



PUS TUBE, PELVIC ABSCESS, ETC. 



203 



PUS TUBE, PELVIC ABSCESS, AND PELVIC PERITONITIS. 

xllmost all that has been said of appendicitis applies equally 
well to these conditions. 



Table XIX., A. — Pus Tube and Pelvic Abscess. 



!^ « O 



Remarks. 



5,400,000 



4,202,000 
4,880,000 



4,544,000 

3,800,000 

5,210,000 
5,120,000 

'5,376,000' 
3,760,000 

5,200,000 
5,200,000 
3,704,000 



5,021.000 
4,400,000 



3,940,000 

3,860,000 
4,592,000 
3,840,000 
5,776,000 
5,000,000 
3,410,000 
5,088,000 
5,184,000 
4,300,000 
3,800,000 



4,656,000 



43,000 
31,000 
45,900 
20,200 
15,200 
12,200 
34,000 
34,000 
34,600 
35,000 
40,000 
17,300 
11,500 
12,000 
32,500 
30,000 
29,200 
28,800 
27,300 
27,000 
25,000 
26,600 
24,400 
24,400 
24,000 
23,000 
22,000 
22,000 
22,000 
21,100 
20,200 
23,800 
20,000 
19,800 
19,000 
21,100 
16,000 
18,600 
19,600 
21,600 
18,200 
16,300 
19,000 

18,800 
18,800 
18,500 
18,000 
18.000 
18,000 
16,400 
18,000 
16,000 
16,000 
15,600 
18,200 
15,600 
15,300 






60 



Double pus tube ; too weak to operate. December 15th. 
December 22d. 

December 29th; abscess burst per vaginam. 
January 4th, abscess opened in groin. 
8th. 
11th. 
Pelvic abscess. 
Pus tube. June 18th. 
June 19th. 
20th. 

27th, fever and vomiting just before catamenia. 
July 1st, temperature normal. 
" 8th, mass decreasing. 
" 14th, slight thickening still. 
Pus tube; septic arthritis; jaundice. 
Pus tube. 
Double pus tube. 
General purulent peritonitis. 
Pus tubes. 

Double pus tube. November 17th. 
November 19th, operated. 
Pus tubes. 
Pus tube. 

Pus tube four weeks' duration. 
Pus tube. 

Pelvic abscess (fetid pus). 
Pus tube. 
Pus tube. 

Pus tube ; operation ; pus found. 
Pus tube operated. 
May 1st. 

" 11th, mass the same; pus tube. 
Pus tube. 
Pus tube. 
Pus tube. 
No fever. 
May 4th. 

" 9th. 
No fever. 

May 18th, flow of pus from os started by manipulation. 
Out doors. 

Pus tube and ovaritis; operation; pelvis full of foul 

pus ; recovery after hysterectomy. 
Pus tubes. 

" tube. 

" tube ; three hours after food. 

" tubes. 

" tube. 

" tube, etc. 

" tube; svphilis. October 7th. 
October 12th. 
Pus ear. 
Pus tube. 

Pus tube. May 8th. 

May 18th, transferred. 

Pus tube ; large amount of pus found. 

Pelvic peritonitis. 



Temperature 99° 
May 2d. 



April 26th. 



204 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XIX., A.— Pus Tube and Pelvic Abscess {Continued). 



36 



38 



,000 



4,310,000 
3,008,000 
4,700,000 



3,910,000 
4,756,000 

4,240,009 



3,800,000 
7.000,000 
4,125,000 



472,000 
5,840,000 



14,975 
12,600 

14,800 
13,853 
12,500 
12,200 
12,200 
12,300 
12.000 
11,850 
13,750 
11,000 
10,600 
11,000 
11,500 
10,400 
10,000 
10,000 
17,000 
13,400 
9,000 
9,200 
7,500 
7,200 



48 



64 



Remarks. 



Pus-tube. July 21st, chills and delirium. 
July 23d. 

" 25tli; operated. 
Pus tube; chlorosis. 
Pus tube. 

Pus tube (double) ; operated. 
Pus tube ; slight. 
Pus tube. June 2d. 
June 10th. 
Pus tube. 

Pus tube. January 5th and 6th. 

Pus tube. Not operated; very slight. 
Chronic salpingitis. June 21st. 
June 25th, better. 

" 29th. 
Pelvic peritonitis. 
Pelvic abscess (?). 
Pelvic abscess. August 28th. 
September 3d, temperature up. 

" 6th, normal temperature. 
Salpingitis, 9 a.m.; 99.4°. 
4 : 15 P. M. ; five days in hospital. 
Pus tubes (small; size of finger). 
Pus tube. 



Increasing counts of leucocytes usually point to the need of 
an operation; stationary leucocytosis to a well walled-off ab- 
scess. The size of the count is a rough measure of the size of 
the abscess, and cases without leucocytosis rarely need operation 
and usually recover under palliative treatment, as also do many 
with leucocytosis. 

Differential Diagnosis, 

Pelvic pain and soreness may be as great in various non- 
suppurative conditions (ovarian neuralgia, etc.) as when 
abscess is present, but the leucocyte count is raised in none of 
the pelvic disorders of women except abscess, septicaemia (puer^ 
peral, after abortion, etc.), and hemorrhage (menorrhagia, 
metrorrhagia, ruptured tubal pregnancy). Endometritis and 
cystitis usually cause no leucocytosis. The application of these 
rules will not infrequently help in the diagnosis of pelvic disease 
and in deciding how much importance to attach to the com- 
plaints of pain, tenderness, etc., in a doubtful case. The ab- 
sence of leucocytosis makes us rightly confident that no abscess, 
of any considerable size exists. 



OSTEOMYELITIS. 



205 



OTITIS MEDIA. 

Most cases, if pumlent, shov/ leucocytosis both before and 
after paracentesis. If serous (see Table XIX., B, cases 2, 7, 8 
and 9) the count is usually lower, and we can predict with 
moderate certainty whether serum or pus will be found on punc- 
turing the drum. When the mastoid is involved the count runs 
higher. If the case drags on, the haemoglobin may get low, 
otherwise the red cells are not affected. 



Table XIX., B.— Otitis Media. 



Adult. 
47 
19 

Adult. 
Adult. 



27 
7 

Adult. 
4 



4,786,000 
4,168.000 
5,120,000 

5,942,000 
4,472,000 
5,416,000 

4,850,000 
4,416,000 
4,100,000 



36,700 
27,300 
34,400 
27,000 
21,000 
16,800 
16,600 
16,480 

8,800 
15,200 
14,750 

9,750 

8,500 
6,400 
4,000 
Marked 
leuco- 
cytosis. 



a o a 
CD .£3 be 



65 



Remarks. 



Nephritis acuta. April 30th. 
May 7th. 

" 14th, otitis only. 

" 22d. 

" 28th, slight discharge still. 
Serous. 

Double purulent; vent not free; mastoid sore. 
April 28th. 
May 5th, well. 
Pus. 

December 7th, hysteria. 

December 25th (during dyspnoeic and cyanotic 

attack). 
Serous. 
Catarrhal. 
Serous. 

Purulent; chronic right, acute left. 
Diff. 116 cells: Adult cells, 57 per 

cent; young cells, 31; eosino- 

philes, 3. 



OSTEOMYELITIS. 

In three cases in which no external opening was present, the 
patient complaining only of pain in the bone, the counts of leu- 
cocytes were 25,600, 24,310, and 18,000, and in each the predic- 
tion that pus would be found was verified at operation. Three 
differential counts in chronic cases with sinuses showed nothing 
remarkable, no increase of the marrow cells or eosinophils . 

The diagnostic value of the blood in osteomyelitis seems to 
me considerable, inasmuch as it is difficult by the symptoms 
alone to feel sure enough of the existence of pus to be willing to 
operate. " Rheumatic pains," " growing pains," and neuralgia 
can be excluded by the presence of leucocytosis. 



206 



SPECIAL PATHOLOGY OF THE BLOOD. 



Othee Abscesses. 

(1) Felon. — It is striking to see how small a collection of 
pus can raise the leucocyte count. Felons containing less than 
one-half drachm of pus may have a leucocytosis of 15,000 to 
22,000. I have counted the blood in three such cases. The ele- 
ment of septicaemia must be considerable. It seems to make 
no difference whether or not the pus is under great tension. The 
leucocyte count does not fall sharply after the felon is opened, 
but gradually diminishes during the next seven to ten days. 
Even a 

(2) Gum boil raised the white cells to 27,000 in one case. An 

(3) Abscess of the vulva showed 23,500 leucocytes per cubic 
millimetre, and an 

(4) Abscess of the vagiim, 12,800. Other varieties are: 

(5) Parotid abscess, 45,500 leucocytes per cubic millimetre. 

(6) Subpectoral abscess, 16,000 leucocytes per cubic milli- 
metre. 

(7) Abscess of the neck, 22,200 leucocytes per cubic milli- 
metre. Carbuncle, 41,000 leucocytes per cubic millimetre. 

(8) Psoas abscess (infected), 50,000 leucocytes per cubic mil- 
limetre. 

(9) Abscess of ovary, 26,000 leucocytes per cubic millimetre. 

(10) One case of perinephritic abscess was watched for some 
days while the patient was getting up strength for an operation. 
It was an abscess of several months' standing, not increasing in 
size during the last month, and the counts, as we should expect, 
did not rise or fall considerably but showed a steady well-marked 
leucocytosis. 

July 29th, white cells, 21,400 
" 30th, " " 21,200 
August 8th, " " 22,400 
" 11th, " " 23,000 
" 24th, " " 22,200. (Operation.) 

A second case counted only showed 16,000. Both abscesses 
contained over a quart of pus. 

A third case, evidently tubercular in origin and probably not 
much infected with pyogenic cocci, showed onl}^ 10,000 white 
cells per cubic millimetre. 



GONORRHCEA. 



207 



(11) Abscess of the Lung. — Three cases following pneumonia 
have occurred at the Massachusetts Hospital within the last 
three years, and the counts happen to be nearly the same. 
Case L, 16,800; Case XL, 16,000; Case IIL, 16,400. 

(12) Subphrenic abscess, also three cases. 



Case. 


Red cells. 


White cells. 


Per cent 
hgemoglobin. 


Remarks 


1 


4,450,000 


53, 267 
25, 600 
15, 500 
17, 600 
22,000 




May 16th. 
" 17th. 
" 20th. 


2 


3 


3,200,000 




55 
38 





Diagnostic Value. 

1. The case of vulvar abscess was so morbidly modest thai 
she complained of all parts of her body except the one diseased 
and gave a train of symptoms which utterly failed to account, 
for the leucocytosis. The presence of this leucocytosis called 
for a much more searching physical examination than would 
have otherwise been made, and the seat of real trouble was dis- 
covered. 

2. {a) The diagnosis between perinephritic abscess and cyst 
of the kidney is materially assisted by the fact that the former 
causes leucocytosis, while the latter (see page 151) does not. 

Q)) Both cancer of the kidney and perinephritic abscess 
cause leucocytosis, but if fibrin is not increased cancer is the 
more likely of the two. This differential mark has served me 
well in two cases. 

(c) Hydatid of the kidney and pyonephrosis are not to be 
distinguished from perinephritic abscess by the blood examina- 
tion. In abscess of the lung the blood gives no information 
that cannot be more easily gained in other ways. 

3. Subphrenic abscess may be confounded with malignant 
disease, both of which may cause leucocytosis ; but the absence 
of any increase of fibrin speaks against the existence of an ab- 
scess. 

GONOERHCEA. 

The red cells are not affected, but in acute cases a moderate 
leucocytosis is present and fibrin is increased. Qualitatively, 



208 



SPECIAL PATHOLOGY OF THE BLOOD. 



the white cells show an increased percentage of eosinophiles 
corresponding to the large proportion of these cells in the ure- 
thral discharge. 

YELLOW FEVER. 

Finlay ^ has lately described what he calls a tetragonococcus 
in cultures from the blood of yellow fever. It was pathogenic 
on inoculation into animals. I have seen no confirmation of his 
observations. Jones ^ found coagulation slow, the red cells iiot 
much diminished but showing decided degenerative changes ; 
haemoglobinuria is common. He makes no observations as to 
the white corpuscles. 

TYPHUS FEVER. 



Ewing ^ in four cases found no leucocytosis. Tumas " found 
no leucocytosis, as the following case shows : 







Day of 
disease. 


Temperature. 


Red cells. 


Per cent 
haemoglobin. 


White cells. 




A.M. 


p. M. 


January 


4th 


4th. 




40.0 




















5th 


5 th. 


39.2 


39.6 


4,440,000 


80 


9,600 


(( 


6th 


6th. 


39.0 


39.5 


4, 220, 000 


77 


4,800 


a 


7th 


7th. 


39.0 


40.0 




ii 


8th 


8th. 


39.2 


39.3 


4,280,000 


77 


3,200 


u 


9th 


9th. 


39.0 


39.5 




u 


10th 


10th. 


38.8 


39.2 


4,440.000 


77 


3,200 


t( 


11th 


11th. 


38.3 


39.3 






i( 


13th 


12th. 


39.0 


39.2 


4,380,000 


80 


1,600 


(( 


13th 


13th. 


38.8 


39.5 


4,780,000 


80 


3,200 




14th 


14th. 


38.7 


39.0 






u 


15th 


15th. 


38.0 


38.7 


4, 960.000 


80 


1,600 




16th 


16th. 


38.1 


38.8 






u 


17th 


17th. 


38.7 


38.6 


4,160,000 


70 


4,800 


ii 


18th 


18th. 


37.7 


38.2 






ii 


19th 


19th. 


36.6 


38.5 


3,820,000 


67 


1,600 


ii 


20th 


20th. 


38.1 


38.3 










21st 


21st. 


37.5 


38.1 


3,450,000 


62 


3,280 


il 


22d 


22d. 


38.1 


37.8 


3,450,000 


60 


3,200 


ii 


23d 


23d. 


37.5 


38.0 




ii 


24th 


24th. 


37.4 


38.0 


3,130,000 


50 


3,200 




25th 


25th. 


37.4 


39.3 






26th 


26th. 


39.2 










Died on the 26th. 











^ Edinbnrs;h Medical Journal, December, 1895. 
2 Journal of the American Medical Association, March 16th, 1895. 
2 Ewing : New York Medical Journal, December 16th, 1893. 
^Arch. f. klin. Med., vol. 41, p. 363. 



TRICHINOSIS. 



209 



On the other hand, Everard and Demoor, ^ and Wilks ^ found 
leucocytosis. 

RELAPSING FEVER. 
(See Blood Parasites, page 331.) 

GLANDERS. 

Christol and Kiener {Comptes Rendus de V Acad, des Sciences, 
November 23d, 1868) reported leucocytosis in glanders. The 
bacilli of glanders can be demonstrated in cover-slip prepara- 
tions of the blood. 

THE BUBONIC PLAGUE. 

In 1895 Aoyoma, a Japanese observer, studied the blood of 
this disease.^ He found the bacilli peculiar to the disease by 
cover-slip preparations from the blood. The red corpuscles were 
not altered. The white corpuscles showed a marked increase — 
20,000 to 200,000(0 per cubic millimetre. This leucocytosis 
was made up almost wholly of adult leucocytes; the eosino- 
phils were markedly diminished, and the blood plates were in- 
creased. 

ACTINOMYCOSIS. 
Ewing (loc. cit.) reports leucocytosis (21,500) in a single case. 

TRICHINOSIS. 

In a case recently studied at the Johns Hopkins Hospital, a 
leucocytosis of 25,000 was present with very great eosinophilia, 
the eosinophiles making up 67.5 per cent of the leucocytes at the 
end of the disease. 

^ Annales de I'lnstitut Pasteur, February, 1893, 
^ Ref. in Sajous' Annual, 1895. 

^ " Mittheilungen aus d. Med. Fac. d. Kaiserlich Japanischen Universi- 
tat," vol. iii., No. 2. Tokyo, Japan, 1895. 



CHAPTEK Y. 



DISEASES AFFECTING THE SEROUS MEMBRANE. 

1. Sekous effusions, representing probably a milder type of 
infection than purulent effusions, liave less effect than the latter 
upon the blood. 

2. The serous effusions, however, must be subdivided into 
the tubercular and the non-tubercular. The former, like most 
forms of tuberculosis (see page 219), rarely raise the leucocyte 
count, while the latter may do so, though in a lesser decree than 
purulent processes. 

Tubercular affections of serous membranes have been dealt 
with elsewhere (page 227) ; but an exception was then made of 
pleurisy, for although there is reason to believe that the majority 
of cases of serous pleurisy are due to tuberculosis, we rarely 
have proof of it, and most observations upon the blood of pleu- 
risy have not been accompanied by bacteriological examination 
of the effusion. Tubercular cases have not been distinguished 
from non-tubercular. Hence the two are necessarily considered 
together here. 

SEROUS PLEURISY. 

Von Limbeck finds in non-tubercular cases from 13,000 to 
15,000 leucocytes per cubic millimetre. The red cells and hae- 
moglobin are not much affected except in chronic cases. 

Rieder finds in non-tubercular cases during the stage of fever 
moderate leucocytosis, 13,000 in one case in which the bacterio- 
logical examination showed the presence of Fraenkel's diplococ- 
cus in the exudation. After the fever has subsided the leucocy- 
tosis falls to, or nearly to normal, so that cases examined for the 
first time some weeks after onset would show no increase at all. 
This he thinks explains the results of Halla and others who 
found no leucocytosis in serous pleurisy. According to Rieder 
the presence or absence of leucocytosis depends not so much 



SEROUS PLEURISY. 



211 



on whether the product is serum or pus as on whether the 
trouble is stationary or advancing. 

In tubercular pleurisy despite fever Eieder found but 4,600 
white cells in one case, and Pick got similar results in two 
cases. 

Hayem makes no clear distinction of tubercular and non- 
tubercular cases and states that "acute inflammatory" pleurisy 
has from 7,500 to 12,000 leucocytes per cubic millimetre. 
The fibrin network is much less dense than in pneumonia; 
in most of the tubercular cases it is not increased at all. 

In fifty-two cases examined at the Massachusetts General 
Hospital the average count of leucocytes was 8,820. 



Table XX.— Pleurisy (Serous). 



No. 


Wiiite 
corpuscles. 


Remarks. 


No. 


White 
corpuscles. 


Remarks. 


1 


24,000 


Pericarditis too ; cy- 


28 


8,000 






anosis. 


29 


8,000 




2 


16,000 




30 


8,000 




3 


15,600 




31 


8,000 




4 


15,000 




32 


7,950 




5 


14,550 


Ill three days. 


33 


7,800 




6 


14,200 


Ill five days. 


34 


7,500 




7 


13,800 


35 


7,000 




8 


13,000 




36 


7,000 




9 


12,800 




37 


6,900 




10 


11,766 


Ill eleven days. 


38 


6,450 




11 


11,600 


39 


6,200 




12 


11,000 




40 


6,100 




13 


10, 900 




41 


6,100 




14 


10,600 




42 


6,000 




15 


10,400 




43 


6,000 




16 


10,000 




44 


5,600 




17 


10,000 




45 


5,600 




18 


10,000 




46 


5,500 




19 


10,000 




47 


5,500 




20 


10,000 




48 


4,800 




21 


9,700 




49 


4,600 




22 


9,500 




50 


4,529 




23 


9,200 




51 


3,400 




24 


8,900 




52 


3,200 




25 


8,800 










26 


8,600 




Aver. =8,820 




27 


8,392 


Ill five days 









Here tubercular and non-tubercular cases are usually not dis- 
tinguished, and a majority of them were not seen till the trouble 



212 



SPECIAL PATHOLOGY OF THE BLOOD. 



had been going on two or three weeks. The patients did not 
seek advice until the effusion was large enough to cause dysp- 
noea. Of the fifty-two cases all but fifteen had no leucocytosis, 
and if the first case, which was complicated with pericarditis, be 
omitted the average count would be only 7,900 instead of 8,820. 
Most of the cases were afebrile or nearly so, and very likely 
tubercular, but no cultures were taken in any. Five cases re- 
acted to injections of tuberculin. None of these five had leu- 
cocytosis. 

The cases luitli leucocj^tosis were mostly those seen in the 
febrile stage, near the beginning of the sickness. No differen- 
tial connts were made. 

In chronic cases the red cells are said to be considerably 
diminished, but this has not been the case in our series; no 
count of under 4,000,000 was recorded and the coloring matter 
was not much diminished. 

Summary. 

1. Red cells and heemoglobin show no important changes. 

2. White cells not increased in most cases except in febrile 
stages, and not often over 13,000 then. Tubercular cases if un- 
complicated probably never have leucocytosis. 

Diagnostic Value. 

The blood count may help a good deal in doubtful cases by 
excluding empyema, pneiimonia, and malignant disease of the 
lung, all of which are accompanied by higher leucocyte counts. 
Compare the average count in serous pleurisy, 8,820, with the 
average in pneumonia, 24,000, or in empyema, 18,300. The few 
counts I have seen of malignant disease of the lung have been 
still higher. 

Hayem insists, rightly it seems to me, that clinicians could 
get real help from blood examination in almost every case of 
doubtful diagnosis in which the lung and pleura are in question. 
In children the leucocytes are considerably increased by even a 
serous inflammation, their blood reacting always more strongly 
than that of adults to any morbid influence, and in them it 
may be impossible to distinguish serous from purulent pleu- 
risy. 



PERITONITIS. 



213 



PURULENT PLEURISY (EMPYEMA). 

The counts in eight cases observed at the Massachusetts 
Hospital are as follows : 



Case. 


Red cells. 


White 
cells. 


Haemo- 
globin, 


Case. 


Red cells. 


White 
cells. 


Haemo- 
globin. 


1 

2 

3 

4 


5,440,000 
6, 000,000 


49, 200 
32,000 
15,200 
14,000 


51^ 


5.... 
6.... 
7.... 
^8.... 


4,850,000 
4,000,000 


12,650 
12,000 
11,100 
10,900 


85^ 


4, 500,000 









This is in marked contrast with serous pleurisy as above 
noted. Yon Limbeck noticed the same thing. 

PERITONITIS. 

A patient with serous pleurisy (non-tubercular) is hardly 
ever in danger, while if the general peritoneal cavity is the 
seat of a like inflammation, recovery is almost out of the ques- 
tion. 

This clinical difference is parallel to the difference in the 
blood condition. Any inflammation of the peritoneum (non- 
tubercular) , whether serous or purulent, calls very large numbers 
of leucocytes into the peripheral blood. The only exceptions to 
this rule are those cases in which the organism is so over- 
whelmed by the disease that it offers no resistance. We have 
seen that this same effect is produced in the severest cases of 
pneumonia and diphtheria, and presumably it is true of many 
other infectious diseases in which the blood has been less care- 
fully studied. 

Almost all cases of general septic peritonitis show very 
marked leucocytosis, and the spreading of a localized process is 
always indicated by an increasing leucocytosis. But here and 
there it happens that the patient cannot react against the disease 
at all, and then the leucocytes are normal or diminished. This 
never occurs in empyema because the system is never so over- 
whelmed by a septic process in the pleura. The fibrin network 



214 



SPECIAL PATHOLOGY OF THE BLOOD. 



is increased in almost all cases. The following counts, all in 
fatal cases, illustrate these points : 



Table XXI. — General Peritonitis. 



No. 


Age. 


Sex. 


1. 


34 


F. 


2. 


Adult 


F. 


3. 


27 


M. 


4. 


Adult 


F. 


5. 


31 


M. 


6. 


Adult 


M. 


7. 


Adult 


M. 


8. 


52 


F. 


9. 


Adult 


M. 


10, 


41 


F. 


11. 







Red cells. 



4,860,000 
7,000,000 
5.317,000 
4,000,000 



,000.000 



5,760,000 
6.840,000 



White 
cells. 



54,000 
32,000 
24.000 
22,000 
19,000 
16,000 
6,000 
5.328 

5,300 
4,600 
Marked 
increase. 



Per cent 
haemo- 
globin . 



95 



Remarks. 



Abscess of spleen (?). 
Purulent; from appendix. 
Dysentery, with perforation. 
Chronic, purulent. 
Ruptured bladder. 
Moribund. 

Purulent; operation. Death. 
Obstruction; died in three days ; au- 
topsy. 

Purulent. Death within 24 hours. 

Purulent. " " " 

After appendix operation. DifE. 1,000 

cells: Advilt cells, 90.5 per cent; 

young cells, 9.5; eosinophiles, 0; 

myelocytes, 1^ 



Diagnostic Value. 

1. When a diagnosis rests between peritonitis and (a) ob- 
struction (non-malignant); (b) malignant disease; (c) hysteria, 
phantom tumors or malingering, the presence of marked leuco- 
cytosis with increase of the fibrin network speaks strongly in 
favor of peritonitis. 

Obstruction or malignant disease ma}' increase the number 
of leucocytes, but rarely increases the amount of fibrin. 
Hysterical or malingering patients have normal blood. 

2. We cannot distinguish serous from purulent peritonitis 
in septic cases, but tubercular peritonitis can always be excluded 
if leucocj^tosis is present. 

3. As to the "chronic granular peritonitis," non-tubercular 
and non-septic, I have seen no reference in haematological litera- 
ture and have no first-hand knowledge. 



PERICARDITIS (WITH EFFUSION). 

As in other inflammations of serous membranes we can dis- 
tinguish the tubercular cases which have no leucocytosis from 
the rheumatic or septic cases which always increase the white 
cells. The tubercular cases are discussed under tuberculosis 



MENINGITIS. 



215 



(see page 230) . The following counts illustrate the rheumatic 
form of the disease : 





Red cells. 


White cells. 


Per cent 
haemoglobin 


Remarks. 


1 




42,400 
32,600 
19,200 
17, 500 

26,000 
19,400 
24, 000 
19,447 
15,400 




November 3d, 1895. 

7th, 1895. 
nth, 1895, 
December 8th, effusion nearly 

gone. 
December 14th. 

" 20th, effusion subsiding. 




















2 


4, 568,000 


67 


3 






4 

5 


4,168,000 


67 











Hay em has noted that pericarditis is far more apt to pro- 
duce leucocytosis than is endocarditis. 



Diagnostic Value. 

In excluding cardiac hypertrophy or simple dilatation with 
ruptured compensation, both of which may occasionally simulate 
a pericardial effusion, the presence of marked leucocytosis is 
absolutely decisive. When we are sure that effusion exists, the 
absence of leucocytosis points strongly to a tubercular process 
as its cause. 

MENINGITIS. 

Leucocytosis is usually well marked. Von Limbeck considers 
that tubercular meningitis can be distinguished from purulent 
by the absence of leucocytosis in tubercular cases, but Osier ' 
states that many cases of tubercular meningitis do have leucocy- 
tosis throughout their course, and my own observations in a few 
cases tend to confirm this. Of Eieder's two cases, one had leu- 
cocytosis and one did not. Zappert's case had 11,130 white 
cells. It seems, therefore, that we sometimes have here an ex- 
ception to the general rule that tubercular processes do not pro- 
duce leucocytosis. Certainly some cases do follow this general 
rule. But however this may be, it is certain that purulent 
meningitis, whether secondary or of unknown origin, is char- 
acterized by high leucocyte counts (Table XXII.), and if in a 

' " Practice of Medicine, " 2d edition. 



216 SPECIAL PATHOLOGY OF THE BLOOD. 

case evidently of meningitis of some kind leucocytosis is ab- 
sent, the case is probably tubercular in origin. 

Table XXII. —Meningitis. 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


1 


Adult. 


M. 


5,900.0«) 


40,000 


2 




M. 


6,400,000 


33,000 


3 


23 


M. 


6,000,000 


27,500 








16,500 


4 


15 mos. 


F. 


5,020,000 


19,500 


5 


7 


M. 


16,000 


6 


26 


M. 




16,000 


7 


20 


F. 




15,784 


8 


2 


M. 




14,200 


9 


22 


M. 


4,356,000 


14,000 


10 


35 


M. 


11,700 


11 


26 


M. 


5,040,000 


11,200 



Per cent 
haemo- 
globin. 




Remarks. 



Diff . 1 , 000 cells : Adult cells, 93 per cent. 

young cells, 7; eosinophiles, 0. 
(Otitis ?) question of tj^hoia. 
March 16th; cerebro-spinal. 
" 18th. 



Autopsy; cerebro-spinal. 
Basilar; no tuberculosis in family; had 
pneumonia. 



Specific. 



Cerebrospinal meningitis (see Cases 3 and 7, Table XVIII. ) 
shows the same characteristics in the blood as do cases limited 
to the cerebral meninges. A case reported by v. Jaksch' had 
4,800,000 red and 24,000 white cells. 

Diagnostic Value, 

Meningitis is the only intracranial disease (except abscess 
and apoplexy) which shows leucocytosis, and this fact may be 
of great help in excluding other causes of coma. 

1. Brain tumor, hysteria, lead encephalopathy, diabetic 
coma, sunstroke, and narcotic or alcoholic intoxication do not 
cause leucocytosis and hence can be excluded by its presence. 

2. Ursemia and post-epileptic coma may have leucocytosis 
and cannot be distinguished from meningitis when leucocyto- 
sis is present; but the absence of leucocytosis excludes men- 
ingitis. 

3. Some cases of typhoid, when seen for the first time and 
without a history of the previous illness, may be difficult to dis- 
tinguish from meningitis, but typhoid never has leucocytosis if 
uncomplicated and meningitis always has. 

4. From pneumonia we cannot distinguish meningitis by the 
blood count. 



1 Zeit. f. klin. Med., 1893, p. 187. 



PART III. 



CHRONIC INFECTIOUS DISEASES. 

CHAPTEE YI. 
TUBERCULOSIS. 

Eed Coepuscues and Hemoglobin. 
(a) Quantitative Changes. 

I. The striking fact is tlie absence of such anaemia as we 
should expect, judging from the pallor of the patients and the 
nature of the disease. It is common to find a normal or even in- 
creased number of red cells in pale cachectic-looking consump- 
tives. We cannot help wondering whether our methods of ex- 
amination are at fault, that is, whether the drop we examine is 
tj^pical. (For discussion of the subject see page 67.) However 
this may be, it is undoubtedly the fact that in most cases of 
tuberculosis, even in advanced stages, the count of red cells is 
approximately normal. Often the haemoglobin is also high. 

n. In a smaller number of cases the haemoglobin is much 
diminished, although the count of red cells is normal — in 
other words, we find the blood characteristic of a moderately 
severe secondary anaemia. The red cells are numerous enough, 
but only because their numbers have been recruited by the influx: 
of "half-baked" or decrepit corpuscles, small-sized and pale, 
poor in albumin and haemoglobin. 

The condition differs from that of chlorosis mainly in that 
some of the red cells are normally developed and nourished, 
while in chlorosis all, or nearly all, are feeble. Such blood oc- 
curs in the severer and more cachectic sufferers from tubercu- 
losis, just often enough to make us wonder that it is not alioays 
to be found. 

TTT. In a small percentage of cases both red cells audi 
haemoglobin are considerably diminished {vide Table XXIII.,, 
15 



218 



SPECIAL PATHOLOGY OF THE BLOOD. 



case 32), tlie latter usually suffering more than do the actual 
number of cells, that is, the color index is usually below 1. 

Von Limbeck^ has recorded a case in which in the course of 
a tubercular process (acute miliary) the red cells fell as low as 
730,000 (white cells, 4,300; haemoglobin, twenty-five percent). 
But the account of the blood is not sufficiently explicit in this 
case to enable us to exclude a true pernicious anaemia in the 
course of which the tuberculosis may have been only the last in- 
cident. No other such case is on record, so far as I am aware. 

(6) Qualitative Changes. 

I. There may be none whatever. 

II. There may be only a pallor of some of the individual 
-corpuscles with slight changes in size and shape. 

III. In very severe cases the poikilocytosis may be extreme, 
but this is much rarer than in many other cachexias of the same 
severity {e.g., malignant disease). 

IV. An important point is the absence of nucleated red cells. 
lExcept after hemorrhages it is very rare to find any nucleated 
Ted cells, and this is in marked contrast with cancer cases, in 
^hich nucleated red cells are the rule. 

V. The degenerative changes described by Maragliano are 
sometimes found in severe cases with mixed infection (vide infra). 

As regards the influence of the different seats of tubercular 
disease (meningeal, pulmonary, genito-urinary, acute miliary, 
«tc.) upon the red corpuscles and hgemoglobin the following are 
the probabilities. 

Pure tubercular disease itself, whatever its seat, has little 
or no effect upon the blood. The widel^^ different conditions of 
ihe blood found in different cases depend probably on the pres- 
^ence or absence of various other organisms (diplococcus lanceo- 
latus, pyogenic cocci) associated with the tubercle bacillus, and 
•on whether there is some drain on the body albuminoids (diar- 
Thoea, peritoneal effusion, starvation, prolonged suppuration). 
When the infection is a mixed one, the blood shows the ordi- 
mary effects of septicaemia (for then the case is practically one 
<of septicaemia) in lessening the number and quality of the red 
<cells. When there is drain on the fluids and proteid constit- 
ments of the body, the red cells may not seem to be diminished, 

' Loc. cit. , p. 336. 



PHTHISIS. 



219 



owing to the concentration of the blood from loss of fluid. Under 
such circumstances they may even seem increased, but the indi- 
vidual corpuscles are sure to be lacking in haemoglobin and the 
other nitrogenous bodies of which they largely consist. 

Fever may be present without there being any changes in 
the red cells that we can detect. It is only septic fever, and not 
the fever of pure tuberculosis that drains the corpuscles of their 
vitality and lowers their numbers. 

Leucocytes. 
(ci) Quantitative Changes. 

Here, as with the red cells, the striking fact is the absence of 
changes in pure tuberculosis. It makes no difference whether 
we are dealing with tuberculosis of the bones, serous membranes, 
or internal organs. So long as the infection remains unmixed 
the white cells are not increased. In certain localities (lungs, 
kidneys) the opportunities for a secondary infection and septi- 
caemia are so great that w^e frequently find evidence of it in the 
blood. On the other hand, psoas abscesses before they are 
opened often contain only tubercle bacilli, and the blood of such 
cases shows no considerable changes. 

So much more is known of the numerical variations of the 
leucocytes in tuberculosis than of the other blood constituents, 
that I shall give a separate account of them in phthisis, in tu- 
bercular bone disease, in tubercular m^ingitis, acute miliary 
tuberculosis, genito-urinary tuberculosis, and tubercular peri- 
tonitis. 

I. PHTHISIS. 

I. In inciinent pMMsis the leucocytes are normal except after 
hsemoptysis. 

n. After attacks of licemoptysis, there is usually leucocytosis, 
subject to wide variations according to the amount of the hemor- 
rhage and the resisting power of the patient. 

This follows the laws of ordinary post-hemorrhagic leucocy- 
tosis {vide supra) and disappears quickly when the hemorrhage 
ceases. 

III. Cavities. — Very constantly accompanied by leucocy- 
tosis. Indeed the absence of leucocytosis in any case proves 
the absence of any cavity of considerable size. 



220 



SPECIAL PATHOLOGY OF THE BLOOD. 



IV. Extensive infltration ("tubercular pneumonia") may 
cause marked increase of white cells, sometimes as great as in 
croupous pneumonia, but this is not invariable. 

Y. Fibroid FJitJiisis (chronic interstitial pneumonia). — As a 
rule the leucocytes show no increase, but if, as sometimes oc- 
curs, we have the combination of this condition with cavity for- 
mation, the latter may increase the count of white cells. 

YI. Fever. — When the temperature is normal the leucocytes 
are normal, but a febrile state may or may not be accompanied 
by leucocytosis (according, presumably, as the fever is or is not 
due to pyogenic organisms). 

YII. Tiibercidin Injections. — At the height of the reaction 
fever the leucocytes almost always rise. 

In a general way, the worse the case the higher the leucocyte 
count, yet the signs may be advanced without causing any leu- 
cocytosis if cavities are absent. 

The following tables give some idea of the range of the counts 
in average hospital cases of phthisis. It is much to be regretted 
that no more than one count was made as a rule in each case. 



Table XXIII.— Phthisis Without Leucocytosis. 



c 




Age. 


Duration. 


Red cells. 


White 
ceils. 


Per cent 
haemo- 


Remarks. 




xn 






globin. 




1 


M. 


48 


4 years. 




6,200 


? 


Fibroid phthisis: extensive; died 














next day : no bacilli. 


2 


M. 


41 


3 months. 




6.500 


? 


^loderate'bilateral signs. 


3 


M. 


56 


2 months. 


4,552,000 


8,200 


105 


Dilated stomach also ; few rales only 
at apices. 


4 


M. 


35 


2 months. 


5,072,000 


5,200 


78 


31ay 5th. Signs very slight. 










4,176,000 


8.800 


60 


May 14th. Two days after a hemor- 














rhage of twenty ounces. 










4,224,000 


9.200 


58 


May 21. 


5 


M. 


22 


2 weeks. 


5,500.000 


8.300 


86 


6 


31. 


31 


1 year. 




6.700 




Tubercular enteritis too. Signs slight. 




F. 


35 


8 months. 




5.700 




Pleurisy. Signs shght. 


8 


M. 


27 


3 months. 


3,600.000 


8.500 


? 


9 


M. 


53 


1 month. 




9.000 


? 




10 


M. 


33 


9 months. 


4,230,000 


7,200 




Intestinal tuberculosis also. 


11 


M. 


27 


Few weeks. 


4,964,000 


9,000 


I 




12 


&. 


26 


8 months. 


3.088,000 


5.200 






13 




20 


2 weeks. 


5,300.000 


9.500 




During hemorrhage. 


14 


M. 


56 


3 months. 




6.4C0 


? 


15 


M. 


31 


5 weeks. 


4,400,000 


6.400 






16 


F. 


27 


4 weeks. 


9,700 




Signs extensive unilateral. No fever. 


17 














Phlebitis (saphenous). 


F. 


26 


1 month. 


3,304,000 


6,200 


48 


Intestinal tuberculosis (?) a 1 s o. 


18 


M. 












Signs very slight. 


21 






5.500 


? 


19 


M. 


51 


1 year. 


4,664.000 


4.800 




With general miliary tuberculosis. 


20 


F. 


? 




4,284.000 


9,750 


58 


21 


F. 


? 


6 months. 


4,400.000 


9.. 500 


63 




22 


F. 


? 


9 


3,986.000 


5.500 


68 




23 


? 


9 


9 


3.336.000 


4.5CO 


55 




24 


M. 


23 


3 weeks. 


5,380,000 


8.250 


83 


No consolidation. Ha9moptysis. 



PHTHISIS. 



221 



TABLE XXIII.— Phthisis Without Leucocytosis {Continued). 



6 


Sex. 


Age. 


Duration. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


25 


M. 


37 


18 months. 


5,080,000 


8,000 


60 


Signs slight. 


26 


F. 


32 


6 months. 


4,120,000 


10,000 


48 


Signs moderate. 


27 


M. 


56 


"Years." 


? 


9,600 


9 


Fibroid phthisis. 


28 


M. 


50 


10 weeks. 


? 


5,400 


? 


Signs slight. 


29 


M. 


31 


4 years. 


9 


6,400 


? 


Fibroid phthisis. 


30 


M. 


30 


8 months. 


5,864,000 


7,200 


66 


No consolidation. 


31 


F. 


19 


12 weeks. 


? 


7,400 


? 


Signs slight. 


32 


F. 


20 


? 


2,732,000 


3,800 


19 



Table XXIV. —Phthisis with Leucocytosis. 



M. 



Age. 



M. 


50 


F. 


19 


M. 


16 


F. 


30 


F. 


55 


F. 


26 


M. 


20 


M. 


32 


F. 


30 


M. 


47 


M. 


30 


M. 


40 


M. 


21 


M. 


30 


M. 


20 




19 


M. 


20 


M. 


72 



34 



Duration. 



1 year. 



1 year. 

2 months. 



7 weeks. 



16 months. 
8 



4 months. 



6 months. 



21^ months 
1 year. 



134 years. 

4 months, 
3 

2 weeks(?) 
8 months. 
1 year. 



Red cells'. 



4,900,000 
3,212,000 
4,608,000 
3,380,000 
3,290,000 
3,870,000 

4,420,000 
7,200,000 
4,364,000 

4,306,000 

5,008,000 



5,880,000 
3,928,000 

5,040,000 
4,488,000 
5,026,000 
5,230,000 
4,384,000 
5,904,000 



5.504,000 
5,300,000 



5,276,000 
4,592,000 



3,820,000 
4,240,000 
4,780,000 
5,100,000 
4,732,000 
4,700,000 
4,200,000 
3,360,000 



White 
cells. 



18,000 
11,500 
11,300 
13,000 
10,500 
13,000 

11,050 
20,000 
18,000 
14,700 
12,500 

22,000 
17,000 
13,000 

18,000 
11,200 

12,000 
12,800 
18,400 
32,000 
17,800 
17,300 
14,000 
13,200 
14,000 
12,000 
12,000 
13,000 
18,400 
13,000 

13,300 
10,600 
10,900 
16,800 
12,700 
13.500 
19,000 
20,000 
15,000 
18,500 
44,500 
22,000 
36,000 
16,400 
20,000 



Per cent 
hasmo- 
globin. 



76 



55 



Remarks. 



Signs moderate; bilateral; "hectic. 



With chlorosis. 
One week later. 



November 22d. 
December 2d. 

During digestion (two and one-half 
hours after supper). 

Signs slight. 

Haemoptysis two years ago. Moder- 
ate unilateral sij^ns. 
Advanced, galloping consumption. 
Intestinal tubercle also. April 6th. 
April 14th. 

Signs slight; time of count not given. 
Extensive signs, both lungs. 
Nephritis too. 
Asthma too. 

Bronchitis and tubercular pneumonia. 
Advanced case. 
Laryngeal tuberculosis too. 

Pneumothorax too. 

Hemorrhage. Signs moderate. 

Advanced case. 

Hemorrhage, one pint to-day, Au- 
gust 29th. 
September 3d. 

Signs considerable; haemoptysis. 
July 10th. With tubercular enteritis. 

" 19th. Chills. 
General miliary tubei'culosis too. 
Slight bilateral. 
Hemorrhage. 
Signs moderate. 
No consolidation. 

Signs extensive. 
Signs moderate. 

Fibroid process with cavities. 
Cavity. Count of white cells once 
7,000 for a few days. 



222 



SPECIAL PATHOLOGY OF THE BLOOD. 



The number of those showing leucocytosis is greater than those 
without it, probably because incipient cases rarely think them- 
selves sick enough to come to a hospital. On the other hand, 
some of the cases which appear to have been going on for months 
have normal leucocyte counts. The duration is less important 
than the nature and severity of the process. It is rare to see 
extensive signs in the lungs without leucocytosis — fibroid 
phthisis excepted. 

Qualitative Changes in the White Cells, 

1. Many cases show none at all. 

2. When the leucocyte count is normal we may find an in- 
creased percentage of young cells (large and small lymphocytes), 
such as is commonly found in any blood poor in nutritive quali- 
ites (see above, page 82) . 

3. "When leucocytosis is present, we usually find the ordi- 
nary marked increase in the percentage of polymorphonuclear 
cells at the expense of the lymphocytes. 

For example: C. D , male, thirty-two years old. Tuber- 
culosis of lungs, with cavities; leucocj'tes, 17,580. Differential 
count of 1,000 cells shows: 

Per cent. 

Polymorphonuclear 83.4 

Lymphocytes (small) 8.2 

Large lymphocytes (large and transitional) 8.4 

Eosinophiles 0. 

4. Eosinophiles are increased during the reaction from an 
injection of tuberculin, and also in some cases with canities in 
which possibly the individual inoculates himself with tuberculin 
manufactured in the cavities of his own lungs. 

Otherwise the eosinophiles are increased only at certain 
physiological seasons — menses and coitus. In most cases asso- 
ciated with leucocytosis they are absent. 

5. Myelocytes were found by W. E. May and myself in four 
cases of advanced phthisis. They averaged .3 per cent. 

Perinuclear Basophilia^ 

Neusser and his followers have advanced a theory that the 
occurrence of perinuclear basophilia during tuberculosis is a 
favorable sign and marks a system capable of resisting the 

^ See Appendix. 



BONE TUBERCULOSIS. 



223 



tubercular infection. Neusser has found this to hold true iu a 
certain number of cases, tending to show that whenever baso- 
philia (the mark of a uric-acid or xanthin diathesis) exists (as 
in gout J bronchial asthma, and leukaemia), tuberculosis rareh* 
occurs. From this he concludes that the presence in the system 
of an excess of alloxan bases (xanthin, uric acid, etc.) makes it 
hostile to the reception or spread of tuberculosis. When tu- 
berculosis does coexist with the uric-acid diathesis (shown by 
perinuclear basophilia) the tubercular process tends to cicatrize 
and heal. 

The theory is interesting and, coming from Neusser, deserves 
careful attention and investigation. If true it might give us in 
tuberculosis a prognostic sign of some importance. ' 

II. BONE TUBEI^CULOSIS. 

Dane's study of the blood in forty-one cases of hip disease 
and Pott's disease is the most complete with which I am ac- 
quainted. Whenever abscesses appeared in connection with the 
disease, cultures were taken when the abscess was first opened 
and again later on, and the coincidence of low counts with ab- 
sence of pyogenic cocci and with high counts of secondary pyo- 
genic infection is very notable. His conclusions are as follows : 

1. " High leucocyte counts, especialh^ in hifj disease, point 
to the probability that there is, or soon will be, abscess forma- 
tion ; but low counts do not preclude the presence of abscess, es- 
pecially in long-standing cases. 

2. "If abscess is present, a low count of white cells indicates 
the absence of secondary pyogenic infection (proved by cul- 
tures) . 

3. " Cases of traumatic origin are generally accompanied by 
a high leucocyte count. 

4. " The leucocyte count bears no direct relation to the tem- 
perature; one case with 30,980 leucocytes (five-year-old girl) 
showed a temperature of only 99.4° at the time of the count. In 

^ Holmes (New York Med. Eecord, September 5th, 1896) described a 
series of changes in the leucocytes which he supposes to be peculiar to 
tuberculosis. W. R. May and I have been unable to confirm these results. 
In part they are not peculiar to tuberculosis. The rest we could not 
satisfy ourselves to be anything more than artefacts. 



SPECIAL PATHOLOGY OF THE BLOOD. 



anotlier girl of three years whose temperature ranged between 
101° and 104°, the leucocytes were only 7,224, or subnormal for 
that age (vide infra, page 336). 

5. " Cases where at the primary operation the pus proved 
sterile show an increase in the leucocyte count when the wound 
becomes infected with pyogenic organisms" (as it always 
•does) . 

6. " The red cells are rarely diminished, but the haemoglobin 
is usually relatively low (mild secondary anaemia in these cases) . 
This absence of a diminution in the red cells in these cases is 
the more remarkable because they were almost all in young chil- 
dren whose blood is much more sensitive to any deleterious in- 
fluence than that of adults." 



(a) As in other forms of tuberculosis there may be none at 
all. (b) The sluggish cell metamorphosis in purely tubercular 
cases is illustrated well by Case 17 of Dane's series, a boy of 
seven whose blood on the day of operation for hip disease with 
large abscess showed 8,982 leucocytes. The differential count 
was as follows : 



Eight ounces of pus were evacuated, in which cultures showed 
the absence of pyogenic organisms. 

This case demonstrates that tubercular suppuration has no 
tendency to produce leucocytosis or to increase in the adult leu- 
cocytes (neutrophiles), but influences the blood only by produc- 
ing what might be termed a functional debility of the blood 
through lack of nutritive substances in the plasma; the 
young cells do not grow up so fast as usual. This condition 
is by no means peculiar to tuberculosis, but occurs in a 
great variety of debilitated or cachectic conditions, as already 
stated. 

(c) But when a septicaemia complicates the tuberculosis, cell 
metamorphosis appears to be accelerated, and we get with the 



Qualitative Changes. 



Per cent. 



Polymorphonuclear neutrophiles 

Small lymphocytes 

Large lymphocytes and transitional forms 
Eosinophiles 



40 
49 
8 
3 



ACUTE MILIARY TUBERCULOSIS. 225 

quantitative increase of leucocytes such qualitative changes as 
the following : 

Per cent. 

Polymorphonuclear neutrophiles 84 

Lymphocytes (small) 9 

Lymphocytes (large and transitional) 6 

Eosinophiles 1 



This was a case (No. 33 of Dane's series) in which the ab- 
scess, sterile when first opened, had become inoculated with the 
staphylococcus aureus. 

{d) Not every case with leucocytosis shows qualitative 
changes as the above. One of Dane's cases (No. 22, a boy of 
seven) showed a leucocytosis of 23,387, but only sixty per cent 
of these were polymorphonuclear, and two per cent eosinophiles. 

In a case recorded by Dane (No. 32) , tubercular osteomyelitis 
showed 6,083 w^hite cells (subnormal, as the child was only two 
years old) with sixty -four per cent of polymorphonuclear cells. 
The pus from the bone cavity showed no pyogenic organisms 
on culture. Ordinary septic osteomyelitis gives very different 
results (see page 205) . Dane's cases were almost exclusively 
hip and spinal affections. 

The following cases from the Massachusetts Hospital records 
illustrate tuberculosis of other bones : 



Case. 


Diagnosis. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


1 


Tuberculosis of the knee ioint 


6,472,000 


9,400 


63 


2 




2,704,000 


8,000 


? 


3 


Metatarsal tuberculosis 


4,650,000 


6,500 


61 


4 




5,016,000 


5,800 


73 



III. ACUTE MILIARY TUBERCULOSIS. 

Probably there are no important changes in the red cells or 
hsemoglobin. The number of cases on record is too small to 
enable me to speak positively on this point, but the acuteness of 
the disease would lead us to expect the normal or approximately 
normal conditions recorded in the few published cases. 

About the leucocytes we know more. 



226 



SPECIAL PATHOLOGY OF THE BLOOD. 



Quantitative Changes. 

Normal or subnormal counts are the rule. When occasion- 
ally there occurs a leucocytosis it may be inferred that the 
miliary process accompanies a suppurative one, and that the 
latter and not the former is responsible for the increased number. 

Warthin^ reports a case with autopsy in which he made over 
thirty counts of the white corpuscles, verifying the more re- 
markable results by repetition. Autopsy showed, besides mil- 
iary tuberculosis, a cavity in the lower lobe of the right lung 
and a suppurating focus about the seminal vesicles containing 
four ounces of pus rich in tubercle bacilli. Whether pyogenic 
organisms were also present is not stated. The leucocyte 
counts were as follows : 



Day. 


Hour. 


Leuco- 
cytes. 


Remarks. 


December 6th 


10 A.M. 


3,500 




12th 


8 A.M. 


5,000 




18th 


5 P.M. 


3,500 




22d 


10 A.M. 


5,625 




22d 


11 :30 A.M. 


4, 725 




22d 


3 P.M. 


5,000 




23d 


5 P.M. 


3,125 




24th 


8:80 A.M. 


3,750 




24th 


11 :80 A.M. 


3,750 




24th 


2 P.M. 


2,500 




24th 


4:30 P.M. 


2, 500 




25th 


8 A.M. 


1,875 


[80 per cent. 


28th 


5 : 30 P.M. 


3,750 


Red cells, 4,125,000; haemoglobin, 


29th 


10 A.M. 


1,250 




29th 


2 P.M. 


1,250 




29th 


5 :30 P.M. 


3,750 




31st 


12 m. 


1,250 




31st 


6 P.m. 


2,500 




January 2d 


11 A.M. 


1,250 




2d 


5 p. M. 


2,500 




8d 


2 :30 P.M. 


600 


Severe chill. Count repeated several 
times. 


5th 


8 :30 A.M. 


3,750 




5th 


11 A.M. 


3,137 




5th 


4 P.M. 


8,125 


Moribund, 


6th 


9 A.M. 


10,000 




6th 


10 A.M. 


5,625 




6th 


11 A.M. 


2,500 




6th 


12 M. 


5,625 




6th 


12:50 P.M. 


Death. 





1 Medical News, 1895. 



TUBERCULAR PERITONITIS. 



227 



In another case lie fouDcl also a subnormal count. Eieder 
found normal counts in two cases. Yon Limbeck states that 
the leucocytes are normal, but gives no counts. 

The following cases from the Massachusetts Hospital records 
illustrate these points : 



Age: 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



18 

40 
14 
51 
12 
37 

36 
80 

Adult. 

22 

36 



8,720,000 
4.664,000 



5,287,000 



600 
750 
400 
800 
100 
800 
200 
600 
257 
457 
000 
700 



23, 000 



Autopsy. 



45 



Phthisis (chronic) also. 

May 14th. 
May 22d. 

Phthisis (healed) also. 
April 18th. 
April 20th. . 

Phthisis with cavities 
also. 

Hypertrophic cirrhosis 



Qualitative Changes. 

So far as I can ascertain Warthin's is the only record of the 
qualitative changes among the leucocytes. In the case above 
quoted, he repeatedly made differential counts of the leucocytes 
by Ehrlich's methods with this average result: 

Per cent. 



Polymorphonuclear neutrophiles 91.49 

Lymphocytes (small) 5.52 

Lymphocytes (large and transitional) 8.09 

Eosinophiles 0. 

Myelocytes 2 



IV. TUBERCULOSIS OF SEROUS MEMBRANE. 
1. TUBEECULAR PERITONITIS. 

The blood condition is exactl}^ as in other forms of tubercu- 
losis, except in so far as it is modified by the drain exerted on 
the blood by diarrhoea or by transudation or exudation into the 
peritoneal cavity. Such events concentrate the blood by with- 



228 



SPECIAL PATHOLOGY OF THE BLOOD. 



drawing water and albumin from it and may give us a normal 
number of red cells per cubic millimetre, when in reality a con- 
siderable anaemia is present. As a rule, the blood shows a mild 
secondary anaemia without leucocytosis or with leucopenia. 
This is exemplified in the following tables from the Massa- 
chusetts Hospital records : 



Age. 



Red cells. 



mite 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



26 
24 

25 



Adult. 

30 

20 
44 
16 
33 
50 
27 

Adult. 
44 
17 



32 
20 

Adult. 

50 
Adult. 
Adult. 

21 



3,120,000 
5, 360, 000 
5,760,000 



4,560,000 



5, 936, 000 
2,974,000 
3,840,000 
4,000,000 
5,240,000 



5,560,000 
4, 904,' 666 



4,200,000 



4,600,000 
5,200, 000 
4,816,000 
3. 550, 000 



2,240 
3,800 
5,600 
3, 900 

5,000 
8,250 
5,183 

5,400 
5,530 
6, 000 
6, 000 
6,400 
6,700 
7,000 
6,800 
7,000 
8,000 

8,200 
8, 500 

No 
increase 
10, 000 
10,000 
11,200 
11,500 



58 



85 



76 



56 



73 
75 



58 



50 



65 



January 6th, 1896. 

April 13th, 1896. 

Starting apparently from tuber- 
cular tube. 

December 18th, 1895. 

January 10th, 1896. 

Starting apparently from tuber- 
cular tube. 

Pleuritic effusion also. 



Glandular tuberculosis also. 
May 22d, 1896. 
May 30th, 1896. 



Tapped ; one hundred and six 
ounces serous fluid obtained. 

Starting apparently from tuber- 
cular tube. 



I know of no differential counts of leucocytes in tubercular 
peritonitis. Presumably the sluggish metabolism of the cells 
found in other forms of pure tuberculosis exists here and causes 
an excess of the mononuclear (young) elements. 

2. TUBEECULAR MENINGITIS. 

Remarkably few counts are on record so far as I can ascer- 
tain. Yon Limbeck gives but a single case (with autopsy). 



TUBERCULAR MENINGITIS. 229 

Four counts, the last on the day of death, showed the follow- 
ing: 

May 32d, 1889 : Leucocytes 8,000 

" 23d, 1889: " 8,000 

" 24th, 1889: " 6,000 

" 26th, 1889: " 7,500 



Rieder records two cases, in one of which the leucocytes were 
"normal or subnormal; in the other increased." In both diag- 
nosis was confirmed by autopsy. The counts in these cases 
were as follows : 



Case L— February 26th, 1891 : Leucocytes 7,800 

March 2d, 1891 : Leucocytes 5, 900 

Case XL— May 30th, 1891: Leucocytes 14,400 

Pick' saw two cases : 

Case L— February 28th, 1890: Leucocytes 6,500 

March 5th, 1890: Leucocytes 8.000 



In the second case there was also no leucocytosis. Autopsy in 
both. Sorensen's' two cases showed respectively 8,300 and 9,400 
leucocytes. My own results in three cases are as follows : 



No. 


Age. 


Sex, 


Red cells. 


White cells. 


Per cent 
hsemoglobin. 


Remarks. 


1 

2 
3 


24 
45 
Adult. 


F. 
M. 
M. 


4,590,000 


6,600 
8,000 
21,500 


46 


Autopsy. 











These are, so far as I can ascertain, the only cases of uncom- 
plicated tubercular meningitis with autopsy in which blood ex- 
aminations are recorded and in all but one of these nothing is 
said about red cells or haemoglobin. Eofcch mentions a single 
case complicated by an appendicitis in which the following count 
is recorded (girl of eleven years) : 

Red cells 5,298,750 

White cells 37,500 

Haemoglobin (per cent) 68 

Whether the leucocytosis was due wholly to the appendicitis 
or not we cannot tell. 



^ Cited by Rieder. 



230 



SPECIAL PATHOLOGY OF THE BLOOD. 



I have examined no other cases of uncomplicated tubercular 
meningitis in which autopsy confirmed the diagnosis. In two 
cases in which clinically the diagnosis was tubercular meningitis 
I found moderate leucocytosis, in one with ninety-one per cent 
polymorx)honuclear cells. Two of the cases of miliary tubercu- 
losis above mentioned had marked meningeal symptoms and 
plenty of tubercles in the meninges, but being a general and not 
a local process no conclusions as to the blood of tubercular 
meningitis can be drawn from the absence of leucocytosis in 
these cases. 

On the whole, although it seems probable that pure tuber- 
cular meningitis, like other pure tubercular processes, has in 
most cases no tendency to raise the leucocyte count, the number 
of recorded cases is still too small to enable us to speak with 
certainty on the point. The red cells and haemoglobin show 
probably the same changes as in other forms of tuberculosis. 

3. Tubercular Pericarditis. 

In one case in which tubercle bacilli were repeatedly demon- 
strated in the fluid obtained by tapping the pericardial sac I 
found no leucocytosis. I have not met with any other reports 
on the blood in this condition. 

4. Tubercular Pleurisy. 

No doubt a large proportion of all pleuritic effusions are 
tubercular in origin, but, so far as I have seen, no counts are re- 
corded in cases proved by culture or inoculation to be tuber- 
cular. The low leucocyte counts in most pleurisies (see above, 
page 211) tend to show that they are tubercular and not due to 
pyogenic organisms. 

Pick mentions that he finds no leucocytosis in tuberculous 
pleurisy when uncomplicated by phthisis, but reports no actual 
counts. 

5. Glandular Tuberculosis. 

In cases of so-called scrofulous glands, whether in children 
or adults, the blood shows no important changes except that in 
children the haemoglobin may be considerably diminished. 



SYPHILIS. 



231 



Leucocytosis is absent unless an abscess has been opened 
and infected. Whether or not tuberculosis, of the abdominal or 
other internal lymph glands affects the blood, I am unable to 
say. 

6. Genito-Urinary Tuberculosis. 

Here the opportunities for a secondary pyogenic infection 
are so good that in well-marked cases we find the blood of 
septicaemia present. The following cases, all involving the 
bladder, kidney, and the external genitals, illustrate this point: 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
hgemoglobin. 


1 


30 


M. 


3,796,000 


14,452 


44 


2 


41 


F. 


3,588,000 


10,400 


55 








3,000,000 + 


14,452 




3 


22 


F. 




10,200 





SYPHILIS. 

Eeiss, in an article in the Arcliiv f. Dermatologie und Syphilis, 
1895, Heft 1, says that the general constitutional influence of the 
poison of syphilis is best indicated by the condition of the 
blood. In one hundred cases he has arrived at the following 
conclusions regarding the 

Bed Cells and Hcemoglobin. 

During the time between the chancre and the secondary symp- 
toms, the red cells are slightly decreased, but this is much more 
marked after the appearance of secondary symptoms and con- 
"tinues for a time even after treatment has begun. The haemo- 
globin sinks steadily from the time of the primary lesion on, 
but is not especially affected by the eruption. Even under 
treatment the haemoglobin 7?ever gets quite up to normal and pro- 
longed mercurial treatment lowers it, although mercury has at 
first a beneficial effect on the haemoglobin as well as on the other 
constituents of the blood. 

Konried ' goes further into detail. According to him, in the 

^ International Derraatological Congress, 1892. 



232 



SPECIAL PATHOLOGY OF TH^ BLOOD. 



first four to seven weeks after infection, the number of red cells 
remains normal, but the haemoglobin begins to fall off, losing 
from ten to twenty per cent in that time. Afterwards it sinks 
steadily unitl treatment is begun, the number of corpuscles also 
falling slightly. 

Newmann and Konried, ' reporting in 1893 on two hundred 
cases, say that up to the time of the secondary symptoms from 
twenty-five to thirty per cent of haemoglobin is generally lost, 
without much change in the red cells, which sink considerably in 
number after the outbreak of secondary lesions. Lezius^ like- 
wise finds no diminution in the number of red cells until the out- 
break of secondary lesions. 

All these changes, like those about to be described, are apt 
to be more marked in women than in men. In cases going on 
to the secondary stage untreated, the haemoglobin may sink to 
as low as twenty -five per cent. In the tertiary stages and in 
hereditary and so-called " constitutional syphilis" the red cor- 
puscles are much more seriously affected, diminishing con- 
siderably in number as well as in weight and color. The 
hereditary syphilis of infancy may indeed produce fatal 
anaemia and Yery low counts are common, with large num- 
bers of nucleated red cells and great deformities in shape 
and size. 

The effect of mercurial treatments on the red cells is interest- 
ing. Gaillard ^ found that the count of red cells increased dur- 
ing the first fourteen days and the haemoglobin during the first 
twenty -four days of treatment. After that time, if mercury was 
still given, the haemoglobin and later the number of corpuscles 
began to decline. 

Konried (loc. cit. ) found the haemoglobin to rise during the 
administration of the first twenty-five to thirty -five inunctions, 
after which it began to go down. This was in cases in which 
treatment was begun just after the onset of secondary symptoms. 
In the worst cases it sank even as low as forty-five per cent de- 
spite treatment, and this usually means a bad prognosis and 
severe tertiary symptoms to come. In one of my own cases the 
haemoglobin was only thirty-seven per cent, though the red cells 
were 4,988,000 (color index, .37). 

1 Wiener klin. Woch., 1893, No. 19. ^ inaug. Dissert., Dorpat, 1889. 
3 Gaz. des Hop., 1885, No. 74. 



SYPHILIS. 



233 



Cases often show spontaneous improvement in their ansemia 
as well as in other symptoms. 

Justus' in three hundred cases claims to have observed a 
peculiar reaction of the hsemoglobin in syphilis, which does 
not occur in any other disease, and which he considers of much 
diagnostic value. 

According to him, if in cases in which secondary symptoms 
have not yet appeared, we test the haemoglobin and then give an 
inunction or a subcutaneous injection of mercury, we find that 
within twenty-four hours a very marked fall in haemoglobin has 
taken place (ten to twenty per cent), owing to the action of the 
mercury on the weakened corpuscles. This sudden fall is fol- 
lowed by a gradual rise until within a few days the coloring 
matter is at a point slightly higher than before the mercury was 
given. In diseases other than syphilis this sudden drop does 
not occur. After the advent of secondary symptoms the pecu- 
liar reaction to mercury does not occur. 

No evidence for or against this observation has as yet been 
brought forward by others. In view of the large number of 
cases in which Justus has tried the experiment it is certainly an 
interesting observation and deserves to be followed up. If true, 
it might give valuable assistance in the diagnosis of doubtful 
cases before the appearance of the "secondaries." 

White Cells. 

1. Here the changes are very characteristic. In the first 
stage the leucocytes are either normal or slightly increased, but 
the percentage of adult forms is almost always notably low, and 
that of the young forms (lymphocytes) high. If mercury is 
given at this stage, the adult forms begin to increase toward 
normal and the young forms proportionately to decrease. [Mer- 
cury given to healthy persons has just the opposite effect, in- 
creasing the young cells at the expense of the adult forms.] 
Iodide of potash works exactly like mercury in this respect, in- 
creasing the adult leucocytes in syphilis, while it diminishes 
them in healthy persons. 

2. As the eruption breaks out leucocytosis (12,750 in one of 
my cases) generally appears, the relative proportions of young 

' Verhandl. d. 5. Cong. d. Deut. dermatolog. Gesellschaft, Septem- 
ber, 1895. 

16 



I 



234 



SPECIAL PATHOLOGY OF THE BLOOD. 



cells and of eosinophiles usually being increased. Treatment 
with mercury and potassium iodide tends to bring down the 
count of white cells, while it raises the count of red ; and among 
the white cells to increase the adult forms. 

In the tertiary stages, with the severe anaemia which is often 
present, there occur occasionally leucocytosis, not uncommonly 
with small percentages of myelocytes, and a marked lymphocy- 
tosis. Miiller' has described four cases of anaemia in syphilis so 
severe as to simulate pernicious anaemia very closely. In one 
the red cells sank to 720,000. Laache'' mentions a similar case. 

There are no constant changes in the blood plates. Specific 
gravity follows pretty closely the haemoglobin percentage. 

Diagnostic Value. 

Justus' reaction of syphilitic blood to mercury, if true, might 
be of great value in distinguishing early syphilis from various 
other causes of debility. 

The occurrence in adults of leucocytosis with increased per- 
centages of young leucoctyes and of eosinophiles, is very sug- 
gestive of syphilis as against tuberculosis, typhoid or malig- 
nant disease. In children, rickets and other diseases may give 
similar blood changes. The chief value of the blood examina- 
tion, however, in syphilis is not for diagnosis but as a measure 
of the stage and severity of the infection. Low haemoglobin and 
high percentages of the young forms of white cells are character- 
istic of severe types. Leucocytosis usually means that the case 
has got beyond the primary stage, while in the tertiary stage 
the presence of myelocytes with a marked anaemia is of serious 
import. 

Certain cases of this last type may closely resemble perni- 
cious anaemia, from which, however, they are to be distinguished 
by their low color index, the frequent presence of leucocytosis, 
and the relative infrequency of megaloblasts as compared with 
the normoblasts, in case nucleated red cells are present. 

LEPROSY. 

Winiarski (Petershurger mediciniscJie JVochenschrift, 1892, 
page 365) gives a careful study of seventeen cases of leprosy. 
^ Charite-Annalen, vol. xiv. ^ j^qq 



LEPROSY. 



235 



He finds in young persons with mild cases no changes from the 
normal blood. 

In severe cases, especially in old people, the anaemia may be 
severe (2,290,000 red cells with fifty-four per cent of haemoglo- 
bin) and even comparable to pernicious anaemia (1,989,000 red 
cells with sixty-three per cent of haemoglobin). In anaemic 
cases the color index is apt to be high, in one case 1.7( !). Such 
severe types are associated with an increase of the average 
diameter of the red cells which explains the high color index. 
The haemoglobin was not relatively low in any case. 

Leucocytes. 

No increase ivas present in any case. Four cases were sub- 
normal. The percentage of young cells, as in other debilitated 
conditions, is often high (forty -five to forty-seven per cent). 



PART lY. 



DISEASES OF SPECIAL ORGANS. 

CHAPTEE VII. 
DISEASES OF THE DIGESTIVE APPARATUS. 

1. (Esophagus (see Malignant Disease, page 287). 

2. Stomach. 

The conditions existing in the stomach may influence the 
blood profoundly in three ways : 

{a) They may be such as to prevent the normal absorption of 
nitrogenous material on which the blood, like all tissues, is ab- 
solutely dependent. Then the blood becomes starved. The 
extreme of this condition is the so-called "atrophy of the 
gastric tubules" which may produce a fatal ansemia. In lesser 
degrees the same process is at work in many forms of chronic 
dyspepsia, gastritis, or chronic starvation. 

Q)) They may lead to severe and repeated hemorrhages. 

(c) They may lead to an auto-intoxication which poisons the 
blood as well as other tissues. 

On the other hand, it is probably through the influence of an 
altered blood serum on the duodenal mucous membranes that 
ulcer of the duodenum is a sequel to severe burns of the surface 
of the body. 

For an account of the influence on the blood of digestion, 
ingestion of liquid, and starvation, see page 83. 

DISEASES OF THE STOMACH 
GASTRIC CANCER. 
(See Malignant Disease, page 287.) 



GASTRIC ULCER. 



237 



GASTRIC ULCER. 
Red Cells and Hcemoglohin. 

A severe anaemia is common. Out of the 28 cases in Table 
XXV., 13, or nearly one-half, had less than 50 per cent of haemo- 
globin, and of the 21 in which the red cells were counted, 5 had 
under 3,000,000 red cells per cubic millimetre. The average 
count of red cells at the time when treatment began was 3,800,- 
000. There is no single disease, so far as I am aware, in which 
the red cells are so apt to be so low, except pernicious anae- 
mia. Even cancer, as a rule, does not fall so low. This is due 
in part, no doubt, to the frequency of hemorrhage from the ulcer, 
but it is not uncommon to see very marked anaemia in patients 
who had never had a hemorrhage. The anaemia is as much 
cause as result of the ulcer ; most probably both are due to a 
common (unknown) cause. 

This anaemia is all the more striking when we remember that 
the frequent vomiting from which most patients suffer tends fo 
concentrate the blood, increase the number of cells in a drop and 
so to make the blood seem less anaemic than it really is. This 
tendency to concentration is probably effective in the cases ob- 
served especially by Oppenheimer, ' in which despite great 
pallor he found normal counts of red cells and haemoglobin. 

It is in such cases that the estimation of the dry residue of the 
blood serum would be of real value could it be made short and simple 
enough for clinical work. Grawitz, who is the prophet of this branch of 
blood examination, gives an interesting case illustrating this point. 

A girl of twenty-five, suffering with peptic ulcer, and exceedingly 
pale, showed on counting the corpuscles 4, 140, 000 per cubic millimetre (no 
considerable reduction), and ninety per cent of haemoglobin. A second 
count showed 4, 340, 000 corpuscles and ninety-one per cent of haemoglobin. 
But the dry residue of the serum was reduced to three-fourths its normal 
amount. The serum suffers in ansemia as much as the corpuscles do. 
Any influence which deprived the serum of one-fourth of its normal solids 
(oedema being absent) must have really affected the corpuscles very much. 
Therefore the corpuscles must actually have been reduced to about 3, 800, 000, 
the reduction being masked by the concentration of the blood from vomit- 
ing. Lymph cannot have run into the vessels and diluted the serum, for 
(owing to the vomiting) the tide is all the other way. If then the serum is 



» Deut. med. Woch. , 1889, No. 42. 



238 



SPECIAL PATHOLOGY OF THE BLOOD. 



reduced a quarter the corpuscles must be so likewise. Unfortunately, to test 
the dry residue of the blood serum requires more time, skill, and apparatus 
than clinicians are apt to have. It is valuable whenever we wish to know 
whether or not an aneemia is being masked by concentration of the blood. 

In severe cases the usual qualitative evidences of secondary 
anaemia (deformities, nucleated corpuscles) are to be found. 



Table XXV.— Gastrio Ulcer. 



c 


? 


X 

0) 


Red cells. 




< 


in 




1 


28 


F. 




2 


52 


M. 


2,031,200 


3 




F. 


5, 024, 000 


4 


20 


F. 




7, 700, 000 


5 


23 


F. 


3,210,000 








A Ann onn 


6 


22 


F. 


4,280,000 


7 


20 


F. 


5,136,000 


8 


55 


F. 


2, 580, 000 








2,100, 000 








3,100,000 








3,620,000 


9 


67 


M. 


3,488,000 








2, 896, 000 


10 


23 


F. 


1,672,000 


11 




F. 


2, 024, 000 








2,464,000 








3,056,000 








3,450, 000 


12 


29 


M. 


1,672,000 








1,560,000 








3,048,000 








3,344,000 



White cells. 



20, 000 



17,200 
12,500 



Per cent 
heemo- 
globin. 



10,000 

9,280 
7, 000 



^800 



8,800 
8,666 
6, 000 
5, 332 
7,500 
7,000 



9,000 
6,000 

5,750 

4,000 

15,500 
(Digestion.) 
8,000 
5,700 
1,800 



^,000 
^600 



80 

95 
30 
82 
77 
88 
90 



65 
25 
35 
40 
55 
51 

52 
61 
72 
62 
40 
25 
46 



42 

37 
40 

25 

30 

36 

48 
20 
15 



33 
58 



Remarks. 



March 27th. Temperature up ; 

no cause known. 
April 15th. 

Hemorrhage and perforation. 

April 23d. 

" 30th. 
May 5th. 
" 14th. Vomiting. 
" 27th. 
January 16th. 
February 1st. 

8th. 
17th. 

August 26th, 7 P.M. Gastric 

ulcer and chlorosis. 
September 2d. 

9th. 
15th. 



One week after, on enemata. 
One month later. 
Ten days later. 

August 13th. Hemorrhage 
one-half pint four days ago 
and same to-day. 

August 24th. 

Hemorrliage one pint the pre- 
vious day ; blood in stools. 

Slight deformities in red cells. 
December 6th. 

Slight deformities. Decem- 
ber 13th. 

No deformities. December 
21st. 

June 4th. No blood. 

*' 18th. Doing well ; slight 

blood in vomitus, none in 

stools. 
July 3d. 

" 17th. 



GASTRIC ULCER. 



239 



Table XXV. — Gastric Ulcer {Continued). 



d 


Age. 


a; 
m 


Red cells. 


White cells. 


Per cent 
hgemo- 
globin. 


Remarks. 


1^ 

xo 


23 


Y. 


K 24.0 OflO 


fiOO 





rGbruary 14tn. 








s: 14.4. 000 




00 


iviaicn /4a. 












4-S 
'±0 


Dtn. 


14. 




F. 


3,460,000 


O, 0\J\J 




Poikilocytosis. 


15 


Adult 


r . 


Cr' ^ /^O AAA 

5, 168,000 


4, 600 


78 


16 


22 


F. 


o 584 000 


4 400 


85 




17 


24 


F. 


q' qoo' 000 


4' 000 


'±0 


■ 












37 


Two weeks later. 












45 


Xill tits 












55 


Five " 












65 


Six " " 


18 


22 


h . 


4, 704, 000 


4,000 


65 




1Q 


22 


F 


f: 1 isja 000 


?! 800 


46 




20 


27 


F.' 


5, 776, 000 


2, 600 


95 




21 






1 OAO f^f A 

1,808, 250 






22 


23 


F. 




00 




9^ 
*o 


37 


f! 






< 0 


OtJJJ ItJlli UtJl Utll. 
















75 


" 18th. 


24 


21 


F. 






103 




25 


24 


F. 






52 


October 10th. 












80 


15th. 


26 


22 


F. 






48 


27 








55 


March 12th. 










65 


" 24th. 






F. 






70 


April 1st. 


28 


17 






50 


May 7th. 








55 


" 16th. 












70 


" 24th. 












70 


April 1st. 












80 


" 8th. 



Hcemoglohin. 

As a rule the color index is low. Only one examination in 
the cases of the Massachusetts Hospital series showed an in- 
creased amount of haemoglobin per corpuscle, and as this was 
not repeated or verified, it may have been a mistake. In all the 
other thirty examinations the color index was low (e.g., Case 5^ 
color index = .39). 

Yet Osterspey records 1,900,000 red cells with 31 per cent 
' of haemoglobin (color index = .81) ; 3,296,000 with 70 per cent 
haemoglobin (color index = 1.09); 4,048,000 with 84 per cent 
haemoglobin (color index = 1.05). Such cases are certainly 
rare. 



240 



SPECIAL PATHOLOGY OF THE BLOOD. 



White Cells. 

Leucocytosis is practicall}' never seen except after hemor- 
rhage and during digestion. When patients who have been fed 
for some time by the rectum are first given food by the mouth, 
the digestion leucocytosis may be very great, as in Case 11 of the 
above series, in which the cells increased from 4,000 to 15,500! 
The presence of a leucocytosis, when the influence of bleeding 
and digestion are excluded, is against the diagnosis of ulcer of 
the stomach. 



Duodenal Ulcer. 



d 


Age. 


X 

a> 
w 


Red cells. 


White 
cells. 


Per cent 
haeino- 
globin. 


Remarks. 


1 


30 


M. 


3,776, 000 


Normal 


50 




2 


47 


M. 


2,100,000 


12,000 


35 


July 24th, much coffee grounds. 










7, 650 




July 29th (five days fasting). 










11,600 




Four hours after meals. 










11,000 




Constant feeding, July 30th. 








2,480,000 


6,000 


38 


August 8th. 








2,630, 000 


6,500 


36 


August 21st, operation. 



These figures are given simply to show that the blood in 
duodenal ulcer undergoes much the same changes as in gastric 
ulcer, and need no further comment. 

ACUTE GASTRITIS AND DYSPEPSIA. 

Acute gastritis or gastro-enteric attacks (Hayem's " emharras 
gastrique") do not affect the red cells or haemoglobin, but are 
very often accompanied by leucocytosis (see Tables XXYI., A 
and B). Where this is the case, it may help us to exclude 
typhoid fever, which has no leucocytosis. Even a twenty-four 
hours' dyspeptic attack may increase the leucocytes notably, as in 
Oases 1 and 2 in Table XXVI., A, and the presence of such an in- 
crease need not make us suspect anything behind the dyspepsia. 
It is probably to be classed as a toxic leucocytosis due to ab- 
sorption of morbid products from stomach or intestine. Fibrin 
may be increased during the period of leucocytosis. 



CHRONIC GASTRITIS. 241 



Table XXVI., A— Acute Gastro-Enteritis. 



1 


A 




Red cells. 


White 
cells. 


Per cent 
hsemo- 
globin. 


Remarks. 


1 

2 


31 


M. 


7,000,000 
5,184,000 


18,000 
15,000 




Well next day. Temp. 104°. 
Well next day. 


13 


F. 


85 


3 


30 


F. 


4,860, 000 


14,200 


80 


Well in tiiree days. 


4 


23 


F. 


6,244, 000 


11,600 


86 


Well in two days. 


5 


17 


F. 


4,600,000 


11,000 


70 


6 


33 


M 


marked 




Well next day. 






increase 




7 


70 


F. 


4,632,000 


10,000 


90 




8 


37 


M. 


4,186,000 


9,200 


68 




9 


57 


F. 




6,000 
5,400 




Temperature 101°. 


10 


23 


F. 


5,144,000 


95 



Table XXVI., B— Dyspepsia and Gastritis. 



Age. 



24 



2 


27 


F. 


3 


26 


F. 


4 


23 


M, 


5 






6 


37 


M 


7 


30 


F. 


8 


41 


M. 


9 


49 


F. 


10 


18 


F. 


11 


60 


M. 



M. 



Red cells. 



6,280,000 

4,750,000 
4, 920,000 
5,0161666 
3,678i666 

4,524,000 



4,200,000 
5,016,000 
3,504,000 



White 
cells. 



22,700 

12,800 
14,000 

11,000 
11,000 
8,924 
7,326 
7,000 

6,000 

4,000 
3,200 
2,800 



Per cent 
haemo- 
globin. 



74 
55 



77 
75 



80 
45 
50 



Remarks. 



Gastralgia ; constipation ; whole 

belly tender. 
Three days later ; well in a week. 
At mealtime, 11,200; four hours 

later, 12,150. 
Dyspepsia. 
Acute gastritis. 

Chronic gastric catarrh. 

Nervous dyspepsia. 

f Before meal, November 1st, 

I 6,000; November 2d, 6,300. 

1 After meal, November 1st, 

t 6,800; November 2d, 7,400. 

Chronic gastritis. 

Dyspepsia. 

Chronic gastritis. 



CHRONIC GASTRITIS. 

(See Cases 6, 9, and 11, Table XXVI., B.) 

Here tlie conditions are different and we never find an in- 
crease of the white cells, but often a decrease due to malnutri- 
tion. Digestion may produce no leucocytosis, or the increase 
may be very slight and late in appearing (four to five hours after 
a meal instead of two to three hours). 



242 



SPECIAL PATHOLOGY OF THE BLOOD. 



Anaemia is very often present and may be extreme. It is be- 
lieved by very liigli authorities that a pernicious anaemia msij be 
caused by chronic gastritis with atrophy of the gastric tubules. 
The writer has never had the good fortune to see such cases. 

The practical points about the blood of chronic gastritis are : 

(a) The not infrequently severe anaemia. 

{b) The not infrequent absence of digestion leucocytosis as in 
gastric cancer, from which therefore the absence of digestion leu- 
cocytosis does not distinguish it. 

The presence of a leucocytosis militates against the diagno- 
sis of chronic gastric catarrh, and, if hemorrhage is excluded, 
points toward cancer. 

HYPERACIDITY AND HYPERSECRETION. 

The leucocytes average higher in these conditions than in 
chronic gastritis or dyspepsia with normal or decreased secre- 
tions (see Table XXVII.). Otherwise the blood is not re- 
markable. 



Table XXVII.— Hyperacidity and Hypersecretion. 



d 


Age. 


i 

xn 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 
3 

4 

5 
6 


Adult. 
30 
40 

40 

28 
57 


M. 
F. 
M. 

M. 

F. 

M. 


5,024, 000 
5,768,000 
5,300, 000 

3,340,000 

4,016,000 
4,160,000 


12, 300 
10,800 
10,000 

7,780 

5,994 
3,600 


82 
82 
85 

76 
34 


Chronic gastritis. 

Slight digestion leucocytosis : 

12, 270 before meal, 14, 300 three 

hours later. 
Dilated stomach ; no digestion 

leucocytosis. 

Lead poisoning and dilated 
stomach. 


Dilated Stomach. 


d 


Age. 




Red cells. 


White 
cells. 


Per cent, 
haemo- 
globin. 


Remarks. 


1 

2 
3 


22 
51 
47 


F. 
M. 
M. 


6,216,000 
4, 184,000 
4,720,000 
5,000,000 
5,264,000 


10,400 
9,600 
8,000 
6,000 
4,600 


83 
55 


Nervous dyspepsia. 
Movable kidney. 


4 
5 


30 
64 


F. 
M. 


75 
70 



DISEASES OF THE INTESTINE. 



243 



DILATED STOMACH. 

In many cases proteid absorption is so faulty that the blood 
is severely starved, but the ancemia may be concealed by the con- 
centration of the blood brought about by the constant vomiting 
of large amounts of fluid. Kussmaul has shown that patients 
often vomit more fluid than tJiey ingest, and it is obvious what 
must be the drain of this process on the fluids of the blood and 
all other tissues. 

Digestion leucocytosis is often absent, as in cancer or chronic 
gastritis. 

CORROSIVE GASTRITIS. 

The blood was examined in a case of this kind in 1895 at the 
Massachusetts General Hospital with the following result : Eed 
cells, 3,792,000; white cells, 32,500; haemoglobin, fifty-three per 
cent. 

DISEASES OF THE INTESTINE. 

Influence of Saline Cathartics on the Blood. 

■ Hay ^ gives the following figures, showing the effect of sul- 
phate of sodium in concentrating the blood : Healthy man of 
thirty-three, 3:35 p.m. Eed corpuscles, 5,025,000; given 85 
c.c. of a concentrated solution of sulphate of sodium in water; 
thirty-five minutes later blood count showed red corpuscles, 
6,540,000; sixty-five minutes later blood count showed red cor- 
puscles, 6,790,000; four hours later blood count showed red cor- 
puscles, 4,930,000. Evidently much fluid was drawn out of the 
blood-vessels and then within four hours the tissues had sup- 
plied the loss and the blood had returned to its normal density. 

Hay also showed that dilute solutions of the same salt had 
far less effect in concentrating the blood. Farther he demon- 
strated that if the blood is already concentrated when the saline 
is given, no purgative effect follows. 

Grawitz confirms these results ; he found also that common 
salt still further concentrates the blood (hence its production of 

' Hay: "The Action of Saline Cathartics." Journal of Anatomy and 
Physiology, 1882, p. 430. 



244 



SPECIAL PATHOLOGY OF THE BLOOD. 



thirst), and cousiders tliat (as this concentiatiou accelerates 
coagidatio/i) tlie honseliold use of salt water as a remedy to stop 
hemorrhage is well founded. 

Table XXVIII. —Enteritis, Colitis, and Dysentery. 



6 


Age. 


XJl 


Eed cells. 


White 
cells. 


Per cent 
hsemo- 
globin. 


1 


45 


M. 


3, 840, 000 


17,000 


50 










l-±, 0\}\} 












7, 700 












8,800 




2 
3 


25 


F 




17,000 




Adult. 


M. 


8 fi04 000 


13 000 




58 


4 


Adult." 


Si' 


4,320.000 


12.400 










2, 732. 000 


10. 600 










4,488.000 


6,000 




5 


39 


F. 


6,776.000 


8.900 


100 


6 


3 


F. 


4,800,000 


7.900 




7 


Adult. 


M 


4,100,000 


7, 560 


72 


8 


27 


M. 


4.872,000 


7, 000 




9 


20 


M. 


5,008.000 


6.460 


39 


10 


26 


M. 


4, 900, 000 


5,300 


80 


11 


65 






5, 200 


80 


12 


40 


F. 


2,996,000 


5.000 


37 


13 


27 


F. 


4,500.000 


5,000 


70 


14 


34 


F. 


3,920.000 


4. 200 





Remarks. 



Chronic dysentery. August 26th. 
September 3d. 

" 5th, dysentery ceased. 
20th. 

Chronic entero-colitis. 
Chronic entero-colitis. 
Ulceratiye colitis. 
Two weeks later. 

Three weeks later ; much im- 
proyed. 

Acute febrile dysentery ; bloody 
I moyements eyery hour. 
Ulceratiye colitis. 
Chronic enteritis. 

" diarrhoea and tetany. 
" diarrhoea (tubercular?). 
Bloody stools ten days. 
Catarrhal entero-colitis. 
Chronic colitis. 
Diarrhoea. 
Chronic colitis. 



ACUTE ENTERITIS. 

Practically the great majority of cases of acute enteritis are 
part of a gastro-enteric attack, and in Table XX'^T!. (see page 
241) the two haye been lumped together. AMiat was said of that 
table (page 240) need not be here repeated. Besides the slight 
leucocytosis there mentioned, we may find in cases in which the 
stools are very watery, a temporary concentration of the blood 
with increased specific grayity and red corpuscles. 

CHRONIC DIARRHCEA. 

(See Table XXATLI.) 

In acute diarrhoea the other tissues respond to meet the loss 
of fluid sustained by the blood, and the blood is soon normal 
again. But when this process goes on long, the body becomes 



INTESTINAL OBSTRUCTION, 245 

SO wasted that the blood must share in the starvation and the 
albuminoids are drained out of it, leaving it watery and poor in 
corpuscles. A patient of Grawitz after years of chronic dysen- 
tery had but 1,880,000 red cells per cubic millimetre, while the 
serum had twice the normal amount of water and half the normal 
amount of solids. 

Cases 1, 3, 4, 12, and 14 of the series in Table XXVIII. show 
similar conditions. The haemoglobin, however, usually suffers 
most and the color index is low. 

Leucocytosis is rare, but does occasionally occur, possibly 
owing to some complication. 



Table XXIX.— Intestinal Obstruction. 



Age. 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



53 
Adult. 



35 

21 

56 

57 
Adult. 

72 
Adult. 



3, 120, 000 
5,568,000 



3, 504,000 

5,150,000 
4,440,000 
4,272,000 
5,800,000 
4,850,000 
5,200,000 
5,540,000 



20,800 
18,860 
18,800 
14, 666 

12,400 

4,100 

12,000 

12,000 
12,000 
11,000 
6,800 
6,000 
4,000 
4,000 



52 
75 



Cancer. 

9th of May, cancer. 
17th of May, cancer. 
No faeces three days. 
No urine two days. 
One day later, no faeces; urine 

drawn by catheter. 
Three days later, bowels moved 

six times. 
Chronic obstruction with hemor^ 

rhage. 

Obstruction (by a band) . 

Cancer. 

Cancer. 



Cholera is discussed on page 184. 
For appendicitis see Abscess, page 195. 



INTESTINAL OBSTRUCTION. 

The only point brought out by Table XXIX. is that the 
white cells may be increased, especially where the obstruction is 
cancerous. Hence the blood count cannot be relied on to help 
US in the diagnosis between obstruction and peritonitis. It is 
more likely that the examination of the amount of fibrin will be 



246 



SPECIAL PATHOLOGY OF THE BLOOD. 



useful, as it is said to he increased in peritonitis and not in ob- 
struction. 

DISEASES OF THE LIVER. 
CATARRHAL JAUNDICE. 

The serum is colored yellow or greenish-yellow and contains 
bile pigments in solution. In mild cases, i.e., where some bile 
goes to the intestine and the obstruction is not long standing, 
the blood is practically normal, as the cases in Table XXX show. 



Table XXX.— Catarrhal Jaundice. 



d 


Age. 


X 

<£> 

an 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


25 


F. 


4,310,000 


10.000 


77 


Acute gastritis. 


2 








10,000 


90 










8,000 


Three days later. 


3 


43 


M. 


3, 896,000 


8,775 


47 


Alcoholic gastritis. 


4 


31 


M. 


4,800,000 


7,500 


65 


6 


53 


M. 


4,340,000 


6,793 


79 




6 


39 


M 


6,200 


83 


Dilated stomach ; lead poisoning. 


7 


M. 


4,996,000 


6,000 


78 


8 


' * 35 * ' 


M. 


4,350,000 


4,900 


85 


Chronic. 



No one of the eight cases shows any leucocytosis and the red 
cells and haemoglobin have not suffered except in the alcoholic 
case in which other causes for anaemia were present. This is 
contrary to the observations of Grawitz, who found constantly 
leucocytosis, but agrees with those of v. Limbeck and Hay em, 
who never found any increase of leucocytes or any other changes 
in the blood count. Coagulation and the amount of fibrin are 
normal. Von Limbeck noticed an ina^eased resistance of the red 
cells to the influence of distilled water and dilute saline solu- 
tions which in normal blood dissolve the haemoglobin. He 
noticed also that the size of the red corpuscles was greater than 
normal, their volume in a given amount of blood being seventy- 
seven to eighty-one per cent {i,e., they take up seventy-seven to 
eighty-one per cent of the room occupied by the drop) while the 
normal is about forty-four per cent. This was in cases with 
only from 4,000,000 to 5,200,000 red cells per cubic millimetre, 
so that it was evidently due not to an overcrowding of the drop 



CIRRHOSIS OF THE LIVER. 



247 



with red cells but to a true increase of size in the individual 
cells. The same fact has been attested from a different point of 
view by the investigations of v. Noorden, who found the solid 
residue increased, and of Hammerschlag ; and Grawitz has noted 
an increase in the specific gravity of the whole blood, though 
that of the serum remained normal. 

Qualitafive Changes. 

Grawitz noted in severe cases that crenation took place much 
more rapidly than usual in freshly drawn blood, and that the 
rouleaux formation did not take place. This latter point was also 
noticed by Hofmeier ^ in icterus of the new-born. Silbermann ^ 
noticed in the same disease great deformities in the size and 
shape of the cells. In severe febrile icterus Weintraud noted 
in the red cells the white spots and streaks with active (molec- 
ular) movements described by Maragliano (see page 71) as en- 
doglobular degenerative changes. 

Summary. 

INormal blood, except for increased size of the red cells and 
some degenerative changes in severe cases. 

Diagnostic Value. 

The constant presence of leucocytosis excludes an uncom- 
plicated " catarrhal" jaundice, and points to the probabilitj^ of 
malignant disease or inflammation (cholangitis, abscess) . Syph- 
ilis and cirrhosis of the liver might show the same condition of 
the blood unless the characteristics of syphilitic blood were very 
marked (see page 234). From a severe cholaemia the absence of 
any marked angemia distinguishes a purely catarrhal case. (For 
the changes in cholaemia see page 252.) 

CIRRHOSIS OF THE LIVER. 

1. Ordinary (Atrophic) Cirrhosis Without Jaundice. 

In the early stages (according to Hay em) neither the red cells 
nor the haemoglobin fall considerably. Most other observers 

1 " Die Gelbsucht der Neugeborenen, " Stuttgart, 1882. 
-"Die Gelbsucht der Neugeborenen." Arch. f. Kinderheilk. , 1887, 
p. 401. 



248 



SPECIAL PATHOLOGY OF THE BLOOD. 



(perhaps thinking chiefly of the later stages) report marked 
anaemia. Wlajew' counted from 3,000,000 to 4,000,000 red cells ; 
V. Limbeck had a case with only 1,500,000. He noted that the 
count might be increased after a tapping in cases with ascites, 
owing to the concentration of the blood from the rapid refilling 
of the belly with serum. Grawitz, on the other hand, noticed 
precisely the opposite effect in a case whose blood before tap- 
ping had been concentrated by cyanosis, the heart's action being 
embarrassed by the ascites. After tapping, when the heart's 
action had become easier and stronger, the cyanosis disappeared 
and the blood count fell from 4,700,000 to 4,300,000. In v. Lim- 
beck's case it rose from 4,680,000 to 5,160,000. The moral is 
that we should draw no inferences from the count of red cells 
soon after a tapping. 

The ten cases in Table XXXI. , A, were all advanced and their 
red cells averaged only 3,580,000 + per cubic millimetre. They 
steadily decrease as the disease progresses, one case getting as 
low as 1,300,000; but the anaemia may be concealed by cyanosis 
and concentration. 

Qualitative Changes. 

Hayem noticed a curious stickiness of the red corpuscles, a 
great tendency to adhere to each other. Von Limbeck looked 
for it, but could never find it. Hayem and Maragliano noticed 
degenerative endoglobular changes in the red cells {" itat cribri- 
forme''), 

Hcemoglobin. 

Usually the color index is low; the average was .66 in the 
ten Massachusetts Hospital cases. 

White Cells. 

Except after recent hemorrhage none of our cases showed any 
leucocytosis, and the average count was 7,240, some cases hav- 
ing notably low figures (2,400, 3,000, 4,500). 

Hayem 's results agree with this. Yon Limbeck makes no 
definite statement on this point. Eosenstein and Wlajew found 
leucocytosis, the latter 12,000 to 17,000. Possibly their cases 
include the forms of cirrhosis icith jaundice in which (see Table 
XXXI., B) the white cells are more often increased. 

' Eef. in Petersburger med. Woch., 1894, No. 43. 



CIRRHOSIS OF THE LIVER. 2-49 

Tlie forms of hypertrophic cirrhosis icitliout jaundice (fatty 
infiltrated liver) are here classed with the atrophic cases whose 
blood has just been described. 



Table XXXI., A.— Cierhotic Liver without Jaundice. 



d 


Age. 


m 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


53 


F. 


2,950,000 
4,' 300,' 000 


16,000 
12,750 
9,088 




ReceDt hemorrhage. 
Liver enlarged ; ascites. 


2 


41 


M. 


55 


3 


48 


M 


4, 992,000 


62 


Recent hemorrhage. 


4 


53 


M.' 


2' 120,' 000 


9,000 


23 


March 15th, 








1,300,000 


7,500 


22 
15 
15 


April 8th. 
April 18th. 
April 29th! 








2,350,000 


6,000 


20 


May 10th. 








2,375,200 


5, 300 


26 


May nth. 








2,450,000 


5,200 


20 


June 10th. 








4, 500, 000 


7,800 


25 


June 16th. 


5 


36 


M. 


3,440,000 


8,320 


46 


Liver enlarged. 


6 


54 


M. 


4,680,000 


5,000 


48 


Liver, atrophic. July 12th. 








4,312,000 


4,000 


62 


July 25th. 


7 


? 


M. 


2,920,000 


4,500 


56 


Liver atrophic. October 30th. 
November 7th, during digestion. 
" nth, during digestion. 








13,400 
15,300 
3,000 














8 


63 


M. 


3,844,000 










6,170 
2,400 




Erysipelas. Died. 
Liver atrophic. 


9 


50 


M. 


3,568,000 


50 


10 


52 


M. 


3,440,000 


2,400 


50 


August 6th. Died September 2d. 



Table XXXI., B.— Cirrhotic Liver with Jaundice. 



d 


Age. 


>< 

0) 

cc 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


38 


M. 


3,400,000 


19,500 


50 




2 


45 


M. 


4, 568, 000 


14,000 


65 


Liver enlarged. 


3 


35 


M. 


5,016,000 


12,000 




Liver enlarged. 


4 


57 


F 






Adult cells, 83 per cent ; young 












cells, 17 per cent. 


5 


36 


M. 


2,064,000 


4, 300 


50 


Jaundice only transient. 


6 


50 


M. 


2,904,000 


2,400 


54 


Autopsy (hypertrophic cirrhosis). 



2. Hypertrophic Cirrhosis w^th Jaundice. 
Red Cells. 

True (biliary) hypertrophic cirrhosis icith jaundice has ac- 
cording to Hayem an intense anaemia in many cases. In others 
17 



250 



SPECIAL PATHOLOGY OF THE BLOOD. 



it has no more effect on the blood than ordinary atrophic cir- 
rhosis. The six cases in Table XXXI. , B, averaged a little lower 
in the count of white cells than the ten atrophic cases, 3,200,000 
as contrasted with 3,580,000. 

Hcemoglohin. 

In a single case of this variety of cirrhosis Hayem found in 
four successive blood examinations a color index of more than 1. 
His counts are as follows : 



Date. 


Red cells. 


White cells. 


Per ceut 
haemoglobin. 


Color index. 


11th 

12th 

loth 


1,599,600 
1,884,000 
1,798,000 
1,971,000 


21.803 
18.082 
15,500 


41 
50 
50 
53 


1.27 
1.39 

1.46 
1.40 



Dried specimens showed an increased average diameter of 
the cells as in pernicious anaemia. The patient died January 
15th and the autopsy confirmed the diagnosis of hypertrophic 
cirrhosis. 

The observations of v. Limbeck of the increased volume of 
the red cells in jaundice may perhaps be another example of 
the condition here noted by Hayem. The presence of bile in 
the blood makes all haemoglobin estimations unsatisfactory. 

Only one of our six cases showed this same condition — Case 
5 in Table XXXI., B. The corpuscles numbered 2,064,000, or 
foity per cent, and the haemoglobin fifty per cent, a color index 
of 1.25. This case was jaundiced at the time of the exami- 
nation. 

I have seen no confirmation of Hayem 's observation by any 
other writer. 

White Cells. 

Leucocytosis is commoner in this than in the other variety 
of cirrhosis. Hanot and Mennier found from 9,000 to 21,800 
leucocytes per cubic millimetre in five cases of hypertrophic 
cirrhosis and an average of 6,600 in ordinary cirrhosis. Leu- 
cocytosis was present in four of the six cases of the Massachu- 
setts Hospital series, the average of all six being 9,000. 



PHOSPHORUS POISONING. 



251 



Diagnostic Value. 

The blood of either form of cirrhosis has no diagnostic value, 
so far as I know, except to exclude abscess and hydatids. If no 
leucocytosis is present, abscess and hydatid cyst can usually be 
excluded. 

HYDATID CYST OF THE LIVER. 

The only observations which I have met with are those of 
Hayem, who states that the blood shows leucocytosis and in- 
creased fibrin. 

ACUTE YELLOW ATROPHY OF THE LIVER. 

Grawitz records a case with 5,150,000 red cells and 16,000 
white cells. 

A single case with autopsy was studied at the Massachusetts 
General Hospital in 1894, the blood showing 5,520,000 red cells, 
12,000 white cells, and sixty per cent of haemoglobin. 

PHOSPHORUS POISONING. 

Taussig,^ V. Jaksch,^ Badt,^ and v. Limbeck^ note an increase 
in the normal number of red cells per cubic millimetre. Taussig 
found 8,650,000 per cubic millimetre ; Badt, 6,400,000, 6,500,000, 
and 6,800,000 in three successive cases; v. Limbeck, 6,500,000 
and 7,900,000. That this increase is not due to concentration 
of the blood through vomiting of liquid is proved by v. Lim- 
beck's last case, in which no vomiting whatever took place. 

The count usually falls to normal within a few days. All 
these changes were verified in thirty -three cases at the Stock- 
holm Hospital in 1892 (see Stockholm Hospital reports for 1892). 

The white cells in v. Limbeck's second case were increased 
to 12,500. In V. Jaksch's five cases the counts were 58,750, 
48,000, 8,000, 4,070,and 3,400. 

^ Arch. f. experiment. Path, und Pharm., vol. xxx. 

2 Deut. med. Woch. , 1893, p. 10. 

3 Dissert., Berlin. 1891. 

4 Loc. cit. , p. 34. 



252 



SPECIAL PATHOLOGY OF THE BLOOD. 



CHOL^MIA. 

When jaundice is intense and long standing, as in complete 
obstruction of tlie bile ducts by gall-stones or tumors, the blood 
is weakened very notably, and hsemoglobin and the count of 
corpuscles fall steadily. Yery little is to be learned upon the 
subject from the literature, but the qualitative changes men- 
tioned under catarrhal jaundice are much more marked, and 
leucocytosis is apt to be present. 



Table XXXII., A.— Gall-Stones. 



No. 


Age. 


Sex. 


Red cells. 


White ceUs. 


Remarks. 


1 


39 


F. 


4, 768, 000 


24,400 


Gall-stone and cholangitis. Operated. 


2 


30 


F. 


4,820,000 


20,000 


Slight cholangitis. Autopsy. 


3 


63 


F. 


4,610,000 


18,800 


4 


40 


F. 


4, 520, 000 


13,000 


No pain ; simple jaundice. 


5 


40 


M. 




10,256 


Enlarged gall-bladder. 


6 


25 


F. 


5,072,000 


8.800 


Jaundice. No fever. 


7 


22 


M. 


3,288,000 


8,000 


Jaundice. 


8 


25 


F. 


4, 900, 000 


8,000 




9 


25 


F. 


2,844,000 


7,400 




10 


37 


F. 


7,300 


October 1st. 










8,200 


5th. 


11 


24 


M. 


4, 320, 000 


4.000 


Jaundice and pain recurrent. 



Table XXXII., B.— Cholangitis. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Remarks. 


1 




F. 


4,800,000 


50,000 


Suppurative cholangitis. 


2 




F. 


6,400,000 


30, 000 


3 




F. 


4, 960, 000 


22,000 




4 


'21' 


M. 


4,976,000 


14,800 


Jaundice and cholsemia. 


5 


65 


M. 


14,186 


Gall-stones ; chills. 


6 








11,000 


October 20th. Operation October 22d. 










Abscess of liver. 


7 


28 


M. 


6,640,000 


9,000 


Catarrhal. 








5, 592, 000 


6,800 




8 


34 


F. 


4, 770, 000 


4,400 


Catarrhal. 



GALL-STONES. 

Netter' and Sittmann'' have found pyogenic organisms in 
cultures from the blood of patients with gall-stones, as have also 
Gilbert and Girode.^ 

1 Progres Medical, 1886, No. 46. 

^ Deut. Arch, f . klin. Med. , 1894, p. 323 

3 La Semaine Med., 1890, No. 58. 



CANCER OF THE LIVER. 



253 



Of the 11 cases of this disease examined at the Massachusetts 
General Hospital 2 were complicated with cholangitis (see Table 

XXXII. , A). Excluding these 2, leucocytosis was present in 
only 2 of 9 cases. The red cells were low in 2 cases (2,800,000 
and 3,900,000). 

The absence of leucocytosis helps us to distinguish the dis- 
ease from peritonitis and appendicitis, and excludes suppurative 
cholangitis. 

CHOLANGITIS. 

Here the leucocytosis is well marked whenever the inflamma- 
tion has got beyond the catarrhal stage (see Table XXXII. , B) 
and helps us to exclude simple impacted gall-stone, with or with- 
out colic. Cancer may or may not produce leucocytosis, but 
does not usually increase the fibrin network; it is said by Hay em 
that cholangitis does increase it. 

ABSCESS OF THE LIVER. 

In all but one of the cases seen by the writer (see Table 

XXXIII. ) the leucocytosis has been very marked. I have 
never been able to account for its absence in that case. 

The blood does not differ from that of cholangitis with sup- 
puration. From cancer it may often be distinguished by the 
absence of increased fibrin network in cancer, while it is always 
increased in suppurations. 



Table XXXIII.— Abscess op the Liver. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Remarks. 


1 


20 


M. 


4, 533,000 


33,200 


January 11th, 1894. 








5,000,000 


48.000 


" 14th. Operated. 


2 


15 


F. 


3, 750, 000 


26,800 


Operated. 


3 


60 


F. 


4,460,000 


18,000 


Operated. 


4 




M. 




12, 600 


5 


'si' 


F. 


3,440,000 


9, 600 





CANCER OF THE LIVER. 
(See Malignant Disease, page 301.) 



254 



SPECIAL PATHOLOGY OF THE BLOOD. 



GUMMA OF THE LIVER. 

Von Jaksch in a single case found red cells, 2,756,000; white 
cells, 6,100. 

DISEASES AFFECTING THE HEART. 
PERICARDITIS. 
(See Inflammation of Serous Membranes, page 215.) 

ENDOCARDITIS. 

In many cases of acute endocarditis the blood shows no 
changes. In others, whatever alterations there may be are cov- 
ered up by those involved in the rheumatic arthritis associated 
with the endocarditis. 

In certain cases, however, particularly in ulcerative or malig- 
nant endocarditis, we may find the signs of a pyogenic infection 
(see page 188). Sometimes pyogenic cocci can be cultivated 
from the blood and if present may he of the greatest value in a 
diagnosis always difficult to make. 

Grawitz goes so far as to say that in doubtful cases repeated 
negative results of cultures from the blood make it unlikely that 
ulcerative endocarditis is present. 

Sittmann ' considers that important help may be given as to 
the position of the primary focus of infection by the nature of 
the organism- present in blood cultures — i.e., the pneumococcus 
pointing to the lung, the colon bacillus to the intestine, etc. 

Red Cells. 

As in all forms of septicaemia marked anaemia rapidly de- 
velops, more rapidly probably than in any other disease. The 
haemoglobin loses about equally with the corpuscles, according 
to most observers — that is, the blood destruction is so rapid 
that the red cells do not get thin before they die, as is usually 
the case, but are cut off in the prime of health. 

Further evidence of rapid blood destruction is seen in the 
haemoglobinaemia often present. 

^ Loc. Git. 



ENDOCARDITIS. 



265 



Eoscher {loc. cit.) records counts of 4,400,000 and 2,750,000, 
both fatal cases. In one case seen by the writer the count was 
3,792,000 with fifty-eight per cent of haemoglobin. 

White Corpuscles. 
Kieder reports a single case showing these variations : 





Temperature. 


White cells 


January 3d, 1891 


105° 


17,000 


3d, 1891 


99° 


13,700 


8th, 1891 


103° 


15,500 


10th, 1891 


101.5° 


18,000 


12th, 1891 


101.5° 


21,300 


18th, 1891 


101° 


18,800 


22d, 1891 


104.5° 


13,000 


February 11th, patient died. 







Pee found leucocytosis. Roscher in two cases found : Case 
I. : 8,800 leucocytes; patient died in two days. Case II. : 16,- 
800 and 12,000. Krebs in one case found: October 27th, 15,- 
500; October 28th, 44,200; the patient died same day. 

Five cases were counted at the Massachusetts Hospital with 
the following results. In one only the fresh blood was ex- 
amined and showed marked leucocytosis ; in the others : 



Case. 


Red cells. 


White cells. 


Per cent 
haeraoglobin. 


Remarks. 


1 




30,100 
15,800 
18,100 
25,700 
27,840 
18,100 
22,000 
12,600 
14,500 
20,400 
24,000 
10,000 




May 27th. 

May 30th. 

June 17th. 

May 22d. 

May 24th. 

May 26th. 

May 28th. 

January 13th. 

January 14th. 

January 16th. 

January 18th ; died. 


2 






3 






4 


3,792,000 


58 



I have no cases of acute benign endocarditis to compare with 
this, so that I do not know whether leucocytosis would be equally 
marked there. 

Diagnostic Value. 

(a) Blood cultures should never be omitted in cases of sus- 
pected malignant endocarditis. When positive thej are of 



256 



SPECIAL PATHOLOGY OF THE BLOOD. 



great value, {h) In excluding typhoid the presence of leucocy- 
tosis is important. 

MYOCARDITIS. 

Whenever stasis and disturbance of the circulation result 
from weakness of the heart wall, blood changes identical with 
those described under Valvular Heart Disease are present. 
Otherwise the blood is normal. 

VALVULAR HEART DISEASE. 

Grawitz divides valvular heart disease into three stages with 
corresponding blood conditions : 

1. Stage of full compensation : blood normal. 

2. Stage of acute failure of compensation: blood diluted 
(Oertel's "plethora serosa"). 

3. Stage of chronic stasis and cyanosis : blood concentrated 
for the most part ; at times diluted as well. 

1. A valvular lesion j^^r se has no effect on the blood. 

2. When compensation fails and blood pressure is lowered, 
"we find {especially in the venous blood) that the fluid from the 
surrounding lymph spaces has made its way into the vessels 
and dilated the blood. The specific gravity falls, red cells and 
haemoglobin are lower than before, while the white cells are un- 
altered, and the plasma is shown to be more watery than before 
as well as of increased quantity per cubic millimetre. All these 
changes are less marked in capillary blood, and hence are rarely 
observed. 

3. If the heart adjust itself partially to the increased work it 
has to do, and to the chronic passive congestion of the internal 
organs and at the periphery, the blood is concentrated, probably 
in part by transudations into serous cavities and lymph spaces, 
and in part by the increased excretion of moisture by the lungs. 
The specific gravity and the number of red cells are increased, 
especially in the capillaries, and to a lesser extent in the venous 
blood (the conditions being just the reverse of those in acute 
heart failure, stage No. 2) . This is the condition usually found 
in heart disease with chronic venous stasis (passive congestion) . 

But this concentrated condition of the blood may be offset 
from time to time by fresh weakening of the heart and lessen- 



VALVULAR HEART DISEASE. 



257 



ing of blood pressure, and the combination of the two conditions 
may result in a normal blood count. 

The condition of concentrated peripheral blood with the count 
of red cells above normal, is that most commonly seen in chronic 
heart disease with stasis. 

Von Limbeck finds that aortic lesions are more apt to show a 
normal or diminished blood count, while mitral disease is more 
apt to be accompanied by the temporary dilutions and long- 
standing concentration above described. He does not explain 
the cause of this. One of his patients with double mitral le- 
sion showed a decrease of 1,170,000 red cells (from 7,500,000 to 
6,330,000) after exertion. When the patient was quiet, the le- 
sion was compensated ; on exertion compensation temporarily 
failed, blood pressure was lowered, and the blood diluted. 

Sadler^ found considerable anaemia in three out of four cases 
of aortic disease, while only two of seven patients with mitral 
lesions showed anaemia. 

Schneider's^ results were similar in that he found the red 
cells normal in the aortic cases and increased in the mitral ones. 

Hayem found anaemia most common in aortic regurgitation, 
especially in young people. 

In the Massachusetts Hospital records out of twelve cases of 
mitral disease five had less than 4,000,000 red corpuscles per 
cubic millimetre. Of three cases of aortic disease all were over 
4,000,000. I think these figures simply mean that the mitral 
cases are more apt to come to the hospital in the stage of acute 
failure of compensation — therefore (see above) with diluted 
blood — while the aortic cases often come while compensation is 
still good and therefore with practically normal blood. 

Tf^iife Corpuscles. 

Almost all writers whom I have consulted agree that the leu- 
cocytes remain normal unless some complication occurs. In a 
certain number of the Massachusetts Hospital cases, mostly 
(but not exclusively) those with cyanosis, the leucocytes were 
increased, the counts ranging sometimes as high as 15,000, while 
the red cells were normal. I suppose this is to be accounted for 
by the fact that in any case in which the circulation is feeble 
and slow, the white cells accumulate at the periphery even more 

^ Loc. cit, p. 33. Inaug. Dissert., Berlin, 1888. 



258 



SPECIAL PATHOLOGY OF THE BLOOD. 



plentifully than the red. This is evidently so in the cases of 
congenital heart disease next to be mentioned, in which the red 
cells are increased only about forty per cent, while the white 
are often one hundred per cent more numerous than normal. 

The apparently normal count of red cells in some of our cases 
was probably due to the covering up of an anaemic or diluted 
condition of the blood by concentration, the resultant of the two 
forces being an apparently normal count. 

Koblank (Jioc. cit.) gives the following cases illustrating this 
condition : 

Red cells. White cells, 

1. Mitral leakage. 5,461,250 28,000 + ; autopsy. 

3. Aortic leakage 4,716,600 13,000 + 

This leucocytosis must be taken into account in making in- 
ferences from cases whose circulations are feeble, and no deeper 
underlying cause {e.g., abscess, cancer) need be assumed to ac- 
count for the increase. 

(Edema and diuresis have in themselves little or no constant 
effect upon the blood, as a recent observation of Petrowsky's 
has demonstrated. 

CONGENITAL HEART DISEASE. 



In the cyanosis accompanying this affection very high blood 
counts are reported. Gibson found : 



Case. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


1 


8,470,000 
6,700,000 


12,000 
12,000 


110 
92 


2 





Carmichael reports, red cells, 8,100,000, white cells, 16,000, 
in a single case, and Toeniessen counted 8,820,000 and 7,540,000 
in two similar cases. In one case entirely without evidence of 
any stasis I counted 8,431,000 red cells per cubic millimetre. 
How such cases are to be explained I do not know; the ordinary 
explanation of concentration of the blood will not hold in cases 
in which no stasis or lack of compensation exists, yet the skin 
is blue and the blood counts are enormous. 

There is no doubt that the peripheral capillaries always con- 



DISEASES OF THE KIDNEYS. 



259 



tain more corpuscles per cubic millimetre than do the veins. 
Numerous reports from various observers agree upon this. 
Whether this is on account of the loss of water by perspiration 
and consequent drain of blood from the skin cai)illaries is uncer- 
tain, but in congenital heart disease both capillary and venous 
blood is overcrowded with coi'puscles and the explanation is 
difficult. 

The most important practical deduction from these data is 
that a blood count in a patient suffering from poorly compen- 
sated heart disease has no value in determining whether or not 
anaemia is present. The actual number of corpuscles in the body 
is not measured by the number contained in a drop of periph- 
eral blood, since anaemia may be effectually masked by con- 
centration or simulated by dilution. 

This holds good equally for any condition involving general 
stasis and cyanosis either from embarrassment of the heart's 
action or otherwise (for instance, pneumonia in certain stage, 
emphysema, displacement of the heart by serous effusions, or 
tumors), or local stasis of the part from which blood is taken. 
Penzoldt ' noted that in old hemiplegic cases, the blood from 
the affected side contained more corpuscles than that from the 
sound side, and the writer has noticed the same thing in a va- 
riety of vasomotor affections involving local asphyxia. 

DISEASES OF THE KIDNEYS. 

Many factors other than the disease itself may influence the 
blood of nephritic cases. For instance, in scarlatinal nephritis 
the long-standing leucocytosis is probably due largely to the 
scarlatinal poison, rather than to the nephritis. The occur- 
rence of large quantities of blood in the urine has the same in- 
fluence as any other hemorrhage upon the blood. 

(Edema as such has apparently very little effect upon the 
blood, but the loss of albumin in the urine tells both on the cor- 
puscles and on the serum, thinning both with consequent lower- 
ing of the specific gravity of the blood. 

1 Berliner klin. Woch., 1881, p. 457. 



260 



SPECIAL PATHOLOGY OF THE BLOOD. 



ACUTE NEPHRITIS. 
1. Bed Cells and Hcemoghhin. 

Whether largely from the loss of blood from the kidneys or 
from other causes, the red cells are often much diminished, but 
the haemoglobin suffers still more. Laache reports an average 
loss of nineteen per cent of the red cells and twenty-six per cent 
of their coloring matter. 

Hayem found no considerable loss of red cells unless the 
urine was hemorrhagic. The following cases illustrate his re- 
sults. 

Case I. — Acute nephritis, ending in recovery. 



Red cells. 

March 17th, 1882 3,069,000 

March 31st, 1883 2,759.000 

April 7th, 1882 2,821,000 

May 1st, 1882, albuminuria ceased. 

May 17th, 1882 3,038,000 

May 31st, 1882 3,689,000 

Case II. — Acute (puerperal) nephritis; recovery. 

Red cells. 

April 6th, 1881 2,945,000 

" 9th, 1881 2,976,000 

" 12th, 1881, no albumin in urine, 

" 13th, 1881 3,137,500 

" 20th, 1881 3,310,000 

Case III. — Nephritis (chronic ?) with hsematuria. 
Red cells 2,821,000. 



(It should be noted that Hayem 's counts are low on the aver- 
age, and the instrument used by him not very reliable.) 

Grawitz in acute nephritis records 3,400,000 red cells at the 
beginning of the third week, and 3,100,000 ten days later. 

Koblank' counted 5,168,700 in a case of acute nephritis with 
oedema. 

Sadler {he. cit.) in six cases of acute nephritis found in two 
cases 3,590,000 and 2,262,000 red cells; in the other four practi- 
cally normal counts. 

Unaug. Dissert., Berlin, 1889. 



CHRONIC PARENCHYMATOUS NEPHRITIS. 261 



Table XXXIV.— Acute Nephritis. 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hsemo- 
globin. 


Remarks. 


1 


56 


F. 




22,200 




Temperature, 102.5° ; gradually 




















falling in course of two weeks. 










14,000 




Sixth day. 










11,900 




Ninth day. 










12,200 




Nineteenth day. 


2 


11 


F. 


4,068,000 


14,000 


52 


Pale and pasty. Anasarca, as- 














cites, and hydrothorax. 


3 




F. 




12,000 




4 


'33' 


M. 


3, 904, 000 


9,300 


50 


Eczema and purpura also. 


5 


22 


F. 


5,000,000 


6,000 




6 


28 


M. 


4, 944,000 


6,400 




Acute parenchymatous. 



In none of the few cases examined at tlie Massachusetts 
Hospital were the red cells much diminished, but in two cases 
the haemoglobin was very low, the color index being .62 in one 
and .61 in the other. 

The blood plates are much increased (Hayem) and fibrin 
slightly increased. 

• 2. White Cells. 

Leucocy tosis is the rule, lasting often for weeks at a time and 
gradually diminishing in convalescence. 

Hayem gives counts of 14,973, 12,400, 15,000, and 13,000. 

Koblank (Joe. cit.) and Grawitz each in a single case found 
normal counts (7,300 and 5,600). 

Sadler found an increase in only one of his six cases, and then 
the highest point reached w^as 13,312. 

Of the six cases of Table XXXIV. leucocytosis was present 
in three, in one of which it was followed for three weeks and still 
persisted. 

CHRONIC DIFFUSE AND CHRONIC PARENCHYMATOUS 
NEPHRITIS. 

Bed Cells. 

In advanced stages the counts may run very low, but more 
often it is chiefly the haemoglobin that suffers through the drain 
of albuminoids from the blood into the urine. 



262 



SPECIAL PATHOLOGY OF THE BLOOD. 



Hay em gives the following figures : 

Case I. — Clironic parencliymatous nephritis. 

Red cells. Per cent hagmoglobin. 

June 20th 4,309,000 43 

July 4th 4,216,000 44 

October 18th 2,945,000 34 



Case II. — Same diagnosis. 

Red cells. Per cent haemoglobin. 

March 6th 2,619,500 36 

8th 2,836,500 36 

23d 2,464,500 27 



Koblank (loc. cit.) in the same disease found 3,291,700 red 
cells in a single case with much oedema. 

Eeinert found 4,050,000 with 50 per cent of haemoglobin and 
3,604,000 with 62 per cent hsemoglobin. 



Sadler : 

Red cells. 

Case 1 4,120,000 

r 2,405,000— November 19th. 
" 2 ] 1,100,000— January 14th. 

( 1,500,000— January 17th. 

" 3 4,300,000 

" 4 4,300,000 

( 3,737,500— June 28th. 
" 5 •] 3,593,700— July 3d. 

( 2,187,500— August 15th. 

r 3,200,000— July 7th. 
" 6 ] 3,257,000— July 22d. 

( 3,137,000— August 21st. 



Grawitz in an acute exacerbation of a chronic parenchyma- 
tous nephritis found 1,928,000 red cells. 

The Massachusetts Hospital cases show a considerable anae- 
mia in seven out of the twenty-eight, or one-quarter of the 
series. Great concentration is probably the cause of the very 
high counts in cases 10, 18, and 22. The majority of cases are 
not far from normal so far as the number of red cells goes, and 
the haemoglobin is also very little diminished; the color index 
is high. 



CHRONIC PARENCHYMATOUS NEPHRITIS. 



263 



Table XXXV 



-Chronic Diffuse and Chronic Parenchymatous 
Nephritis. 



d 


Age. 


>i 






02 


1 


Adult. 


M, 


2 


45 


M. 


Q 
O 


'±o 


M 


4 


43 


M. 


5 


56 


F. 


6 


66 


M. 


7 


27 


M. 


8 


23 


M. 


9 


59 


M 


10 


44 


M. 


11 


49 


M. 


12 


43 


F. 


13 




M. 


14 


27 


M 


15 


28 


M. 


16 






17 


41 


M. 


18 


8 


M. 


19 


39 


M. 


20 


7 


M. 


21 






22 


Adult. 


M. 


23 


30 


F. 


24 


30 


M. 


25 


58 


M. 


26 


Adult. 


M. 


27 




M. 


28 


19 


M. 



Red cells. 



2,648,000 
4,400, 000 
5,480,000 
4,940, 000 
5, 600, 000 
4,912,000 
4, 380,000 



6, 936, 000 
4,844,000 
4,196,000 
3, 780. 000 



6,000,000 
3, 564, 000 
5,456,000 
6, 800, 000 
4, 552, 000 
3,160,000 
4, 572,000 
1,055,555 
3,040,000 
4, 756,000 
5,512.000 

3,256,000 
3, 560,000 
5, 900,000 



White 
cells. 



18,600 

16,300 

15,000 
14,500 
14,000 
14, 000 
13,000 
12,500 
26,800 

12,100 
11,300 
11,000 
10,800 
7,750 
13,600 
9,000 
7,600 
7, 332 
7,000 
6,800 
6,500 
6,400 
6,250 
5,513 
5,200 
5,000 
4,800 

4,500 
3, 000 



Per cent 
haemo- 
globin. 



45 

55 
88 
90 
85 
64 
54 



82 
78 
50 
60 



75 
60 
65 
40 

85 

54 
65 
62 

51 
64 
82 



Remarks. 



Stasis and cyanosis ; arterioscle- 
rosis. 
Universal eczema. 
Uraemia. 

Ascites, hydrothorax, asthma. 
Ascites, hydrothorax. 
Adult leucocytes, 72 per cent. 
Much fat in urinary sediment. 
Uraemia, April 3d. 
Convulsion and coma, April 16th. 
April 17th, died. 
Uraemic ; vomiting. 
Diarrhoea for five months. 
Uraemic and moribund. 

December 28th. 
January 21st, uraemic. 



(Edema (!) 



Double aortic murmur ; hydro- 
thorax. 

Asthma. 



White Cells. 

Hayem records 25,000, 19,000, 13,000, 10,000, and 6,000 and 
concludes that tlie counts vary mucli not only in different cases 
but in the same case at short intervals. 

Koblank found 14,700 in a single case. 

Sadler in one case found 6,300 in November and 16,000 in 
the following January ; 12,000 in another case ; 8,800, 7,700, and 
1,916 in others. 

The same wide range is seen in Table XXXV., in which 



264 



SPECIAL PATHOLOGY OF THE BLOOD. 



thirteen of the twenty -eight cases showed leucocvtosis. Of 
these thirteen six were uraemic. The presence or absence of 
oedema seemed to make no difference. 



CHRONIC INTERSTITIAL NEPHRITIS. 

Haj'em found the fibrin more increased in this form of ne- 
phritis than in am^ other, and the antemia less pronounced. 
Grawitz distinguishes two stages : 

I. As long as the heart is strong enough to overcome the in- 
creased resistance at the periphery and the disturbances of cir- 
culation are not marked, the blood is normal. 

II. When compensatory hypertrophy is no longer sufficient 
to do the work of forcing the blood through the system, the 
usual effects of failing compensation (see Heart Disease, page 
256) appear (dilution and subsequent concentration of th?. 
blood). 

The ivliite cells are normal. 



Table XXXVI., A.— Chronic Interstitial Nephritis. 



6 


Age. 


X 

(E 
72 


Red cells. 


White 
cells. 


Per cent 
hteiiio- 
globin. 


Remarks. 


1 

2 
3 

4 

5 


39 


M. 
F. 
M. 


6,040,000 
4, 548,000 
4,244, 000 


19,381 
15,000 
12,000 

9,724 
6,000 


80 
50 
67 


Uraeniic coma ; moribund. 
Uraemic ; mitral stenosis. 
Three and one-half hours after a 

meal. 
Uraemic ; moribund. 
March 23d. 
" 30th. 


Adult. 

46 
20 




4,088,000 


66 
52 


Table XXXVI., B. — Pyelo-Nephritis. 


6 
1 

2 
3 
4 


Age. 


X 
a> 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


24 

26 
33 
26 


F. 

F. 
M. 
F. 


3, 056, 000 
2,976,000 
2, 696, 000 
3,272,000 
4, 200, 000 
4,536,000 
2, 356,000 


21,200 
15,200 
18,800 
25, 200 
16.800 
15,550 
7, 280 


41 

38 
33 
33 


March 10th. Uraemia. 

" 13th. 

" 27th. 
April 14th. 

Perinephritic abscess too. 
Cystitis also. 


36 
65 



STONE IN THE KIDNEY. 265 



Table XXXVI., C. -Cystic KID^^EY. 



c 


Age. 


0) 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


55 


M. 


3, 664, 000 


6,400 




Adult cells. 72 per cent. Sup- 
posed cancer. Enormous firm 
tumor on each side. Autopsy. 







The cases recorded in Table XXXVL, A, are probably not 
inconsistent with these rules. Of the four cases with leuco- 
cytosis three were uraemic, and in the fourth the influence of 
digestion is seen. The haemoglobin is lower than we should 
expect from Gra,witz's account. 

Uraemia, it would appear from these tables, may cause leu- 
cocytosis or at any rate is not infrequently associated with it. 



PYELONEPHRITIS. 

Table XXX^T!. , B, speaks for itself. The ancemia is often 
severe and leucocytosis is the rule. 



STONE IN THE KIDNEY. 



(See Table XXXYH., A.) The state of the blood depends 
on the amount of ulceration caused by the stone ; when this is 
considerable we have leucocytosis. 



Table XXXVII., A.— Stone in the Kidney. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


19 


M. 




15,200 
14, 750 
9,000 
8,990 
8,000 
8,000 




Much pus in urine. 


2 
3 
4 


'25* 

48 


M. 
F. 
M. 


4, 350, 000 
4,160,000 


78 
65 


5 
6 


58 


M. 


5,680,000 
4, 340, 000 
6, 100, 000 
3,048,000 




Much pus in urine. 
Two weeks later. 








16,500 
7, 500 




7 


52 


M. 


30 



18 



266 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXVII., B.— Floating Kidney. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


37 


F. 


5,056,000 


9, 200 


75 




2 


41 


F. 


4,684,000 


9,000 


75 




3 


23 


F. 


5,400,000 


6,000 


69 




4 


43 


F. 


4,700,000 


2,400 


76 




5 


38 


F. 




75 


Aneurism of arch also. 


6 


24 


F. 






80 







Diagnostic Value. 

Cancer would also cause leucocytosis, but would not increase 
fibrin as a rule, while most cases of stone with ulceration do 
increase fibrin. 

FLOATING KIDNEY. 

The blood is normal. This fact has some diagnostic value; 
for example, when we confound appendicitis with floating kid- 
ney, as has been done (see page 201) . The presence of leucocy- 
tosis excludes the latter and favors the former. Most tumors 
or abscesses with which a floating kidney might be confused 
<30uld be distinguished by the same criterion. 

DISEASES OF THE LUNGS. 
BRONCHITIS. 

" Acute catarrhal and chronic purulent bronchitis have rela- 
tively little leucocytosis in most cases" (v. Limbeck). 

Except for this and a few other passing references, there is 
liardly anything in literature on the blood in bronchitis, so that 
I shall be forced to base my statements chiefly on the few counts 
recorded at the Massachusetts General Hospital. 

1. ACUTE BRONCHITIS. 

Aside from "capillary bronchitis," cases are not infrequently 
seen in which the signs are simply those of general bronchitis 



ACUTE BRONCHITIS. 



267 



of the finer tubes, yet tlie symptoms are much more like pneu- 
monia. Whatever may be the real conditions in the lungs of 
such patients, their blood is not infrequently exactly like that 
of pneumonia and does not help at all in the differential 
diagnosis between the two diseases (see Cases 1 and 2, Table 
XXXVIII., A). 



Table XXXVIII., A.— Acute BRONcmTis. 



d 


Age. 




Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


70 


M. 


4,420,000 


41,000 


70 




2 


56 


F. 


4,800,000 


26,000 


65 


Temperature 103°. Rales on both 














sides alike ; no consolidation. 


3 


Adult. 


F. 


4,192,000 


15,000 


65 


November 5th. 










11,300 




16th. 










17, 600 




25th. 


4 


28 


F. 


6,096,000 


12.000 


65 


Cyanosis? Much purulent expec- 














toration. 


5 


42 


M 




9,300 




Asthma, 


6 


Adult. 




5,260,000 


8,000 


72 


Neurosis. 


7 


50 


M. 


5,952,000 


7,992 


50 




8 


59 


F. 




6,800 




Emphysema. 








9 


36 


M. 


4,392,000 


6,000 


72 


October 31st, 










8,600 




November 3d. 



Table XXXVIII., B.— Chronic BRONcmTis. 



d 


Age. 


1 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks, 


1 


Adult. 


M. 


3,680,000 


18,500 


63 




9 


48 


M 




15,000 




Chronic febrile, with laryngitis. 








Recovery. 


3 


27 


F. 


5,384,000 


8,800 


73 


Constipation ; neurasthenia ; two 












weeks afebrile. 


4 


61 


M. 


4.300,000 


8,000 


63 


Five months. 


5 


20 


F 




7, 925 


78 




6 


18 


M 




7,792 


Keratitis, conjunctivitis. No 




















symptoms. 


7 


26 


F. 


4,700,000 


6,700 


70 


Asthma, 


8 


29 


F. 


4,100.000 


5, 500 


61 


Empyema of the antrum. 


9 


20 


M 


5,062 




One month. 









In the majority, of acute cases, however, the blood shows no 
changes unless concentration due to cyanosis be present (see 
Cases 4 and 7, Table XXXYIII., A). 



268 



SPECIAL PATHOLOGY OF THE BLOOD. 



In ckronic cases (Table XXXYIII., B) leucocvtosis is 
very imcommon, more so, I think, than the table represents. 
If more counts were added, nearly all, I think, would bo 
normal. 

The red cells and haemoglobin show no changes to speak of 
in either acute or chronic cases. 

The blood has no diagnostic value so far as I know except 
that when pneumonia is in question a normal count of white 
cells speaks against it and in favor of bronchitis. If emphy- 
sema is also present it sometimes produces a different blood 
condition from that of simple bronchitis. 

EMPHYSEMA AND ASTHMA. 

Grawitz reports an increase in the number of red cells in 
emphysema, which he believes to be due to cyanosis and to cover 
up the really anaemic condition of the blood of many patients. 
Practically the same conditions are present as in the cyanosis of 
heart disease (see page 256) and the concentration of the blood 
is brought about in the same way. Leichtenstern ^ noticed a di- 
minution in hEemoglobin at the time when the heart first fails, 
due probably to the diminished blood pressure which allows the 
lymph from neighboring tissues to flow into the vessels and 
dilute the blood. 

In both asthma and emphysema it has been noted by 
Miiller, ' Gollasch, ' Gabritschewsky and others that eosinopMles 
are very numerous in the sputum, and Fink ^ also noted an in- 
crease of the same cells in the blood, running as high as 14.6 
per cent instead of the normal one to two per cent. This increase 
is present only at the time of the paroxysm and for a short time 
before and after it. Their presence in increased numbers before 
a paroxysm makes it possible to predict its coming (v. Noorden, 
Schwerskewski) . As this applies only to pure hroncJiial asthma 
and not to cases secondary to disease of the heart or kidney, 
Schreiber states that we are enabled to distinguish bronchial 
from cardiac or renal asthma by the increase of eosinophils in 

1 "Ueber das Hb-Gehalt des Blutes," etc., Leipzig, 1878. 

2 Ref. in Fink, "Beitrage z. Kennt. des Eiters," Dissert, Bonn, 1890. 

3 Fortschritte der Med. , 1889. 

^ Arch. f. exp. Path, und Pharra., 1890, p. 83. 



EMPHYSEMA AND ASTHMA. 



269 



the blood and sputa in bronchial cases, which does not occur in 
asthma due to cardiac and renal trouble. 

For Pneumonia, see page 159. 

For Phthisis, see page 219. 

For Abscess of Lung, see page 207. 



PART V . 



DISEASES OF THE NERVOUS SYSTEM, CON- 
STITUTIONAL DISEASES, AND HEMOK- 
RHAGIC DISEASES. 



CHAPTEE VIII. 

DISEASES OF THE NERVOUS SYSTEM. 
NEURITIS. 



In a single case of multiple neuritis, febrile and apparently 
of an infectious nature, the following counts are found in the rec- 
ords of the Massachusetts General Hospital : 



Date. 


Temperature, 


Red cells. 


White 
cells. 


Per cent 
haemoglobin. 


July 10th . . . . 


101° 


4,816,000 


25.000 
24,800 
18,700 
21,000 
16,000 
28,700 
19, 500 
23.200 


42 


" 13th 




" 16th 








" 20th 








" 25th 




4,320,000 


60 


" 31st 




August 7th 








" 20th 

















The patient, a boy of eleven, recovered and left the hospital 
well. 

But these changes occur also in alcoholic (afebrile) ueuritis, 
as the following counts show. 



Case. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


1 


3, 608,000 
3,260,000 


15, 000 
14,000 


75 


2 


64 





GENERAL PARALYSIS OF THE INSANE. 



271 



In both cases the counts were made just at mealtime, so tliat 
the leucocytosis is not due to digestion. Gastritis was not 
present in either case. 

One case of post-diphtheritic neuritis in a child of eight 
showed the presence of anaemia only : Red cells, 3,850,000 ; white 
cells, 7, 393 ; haemoglobin, 70 per cent. 

Neuritis in lead poisoning does not affect the count of leuco- 
cytes. 

Neuralgia, whether facial, intercostal, sciatic, or ovarian, 
showed normal blood in numerous cases examined at the Massa- 
chusetts Hospital. 

DISEASES OF THE BRAIN. 

Meningitis (see Inflammation of Serous Membranes, page 215). 
Zappert in one case of hraiii abscess found only 4,000 white 
cells. 

In pachymeningitis hcemorrhagica and cerebral syphilis (one 
case of each) v. Jaksch found leucocytosis. 

Cerebral and cerebellar tumors have no effect on the blood as 
far as could be judged from four counts in the former and two in 
the latter disease. Von Jaksch found slight leucocytosis in two 
cases of brain tumor and one of cysticercosis. Zappert found 
normal blood in one case of cerebral tumor. 

CHOREA. 

Chorea showed in five cases normal blood except for increased 
percentages of eosinophiles, as in Zappert' s two cases. 

DISEASES OF THE SPINAL CORD. 

Chronic diseases of the spinal cord, such as tabes dorsalis, 
syringomyelia, spastic paraplegia, diffuse myelitis, paralysis 
agitans, and progressive muscular atrophy, are found to pro- 
duce no changes in the blood. 

For Spinal Meningitis, see page 216. 

GENERAL PARALYSIS OF THE INSANE. 

Capps* has made a careful study of the blood in nineteen 
cases and comes to the following conclusions : 

^ American Journal of the Medical Sciences, July, 1896. 



272 SPECIAL PATHOLOGY OF THE BLOOD. 



1. Red corpuscles and hsemoglobin are always slightly dim- 
inished, the averages being 4,789,900 and 85 per cent. 

2. Most cases show a slight leucocytosis — 22 per cent above 
the normal on the average. Early cases may have no leucocy- 
tosis. 

3. The differential counts show that the blood is slightly 
older than that of normal adults. The adult leucocytes average 
nearly 74 per cent and the smaller forms of young cells only 14.2 
per cent, while the larger forms of young cells (large lympho- 
cytes) are relatively numerous, averaging 7.8 per cent. In a 
few cases the eosinophiles were very numerous' (8.7 and 6.4 per 
cent) . 

4. At the time of convulsions the red cells and haemoglobin 
are apparently increased (due no doubt to the violent muscular 
contractions which raise blood pressure and concentrate the 
Hood, or to cyanosis). 

There is a sudden and pronounced increase in the leucocj' tes 
•during and after convulsions or apoplectiform attacks. That 
this is not due to concentration of the blood or to stasis Capps 
thinks is shown by the fact that not only the number but the 
differential count of white cells show changes, the " large mono- 
miclem^' cells being relatively increased, sometimes as high as 25 
per cent. Myelocytes were seen in one case after the convulsions, 
and especially just before death when in a leucocytosis of 18,250 
11 per cent were myelocytes." 

HYSTERIA AND NEURASTHENIA; HYPOCHONDRIASIS. 

A large number of cases have been counted at the Massa- 
chusetts General Hospital, with a view to excluding other 
diseases. The blood count is always normal except that in a 
certain number of the hysterical cases eosinophiles are rela- 
tively increased, and that many of the neurasthenics show the 
increased percentage of young leucocytes which I have alluded 

1 Roncoroni (Archiv. di Psichiat. Scien. , 1894, p. 293) finds eosino- 
philes increased even to twenty -five per cent in the agitated and violent 
cases. 

2 Leucocytosis has been repeatedly noticed in convulsions from various 
causes. Probably the irritant which causes the motor discharge also acts 
on the leucocytes by chemotaxis. 



MENTAL DISEASES. 



273 



to above (page 82) as characteristic of a variety of debilitated 
conditions. 

Marhed anoemia is seldom present, altliougli the haemoglobin 
is not infrequently as low as 65 per cent. Eeinert ' found the 
haemoglobin under 60 per cent in only 4 out of 48 cases of hys- 
teria, and in none of 36 neurasthenics. 

The value of the blood examination in such cases, like that of 
the urine or the lungs in hysteria, is as negative evidence, and in 
this respect it is important. When the discrepancy between 
complaints and signs is great, we want to be doubly sure that 
nothing hidden escapes our notice, and the blood examination is 
one of the most valuable adjuvants we have in the discovery of 
deep-seated inflammation or malignant disease, as well as in 
giving us a general measure of the patient's degree of bodily 
health as distinguished from nervous force. The former may 
be high when the latter is low, or both may be low, and the dis- 
tinction marks out two classes of cases in which somewhat dif- 
ferent treatment is appropriate. There is no use in undertak- 
ing to make " blood and fat" when the patient has already plenty 
of each, though it may be well to carry out the same regime as a 
matter of suggestion. 

MENTAL DISEASES. 

The association of anaemia with insanit}^ is too frequent to be 
a mere coincidence, though it is hard to make either serve as a 
cause for the other. Very possibly they should both be looked 
upon as symptoms of a common underlying (unknown) cause. 

This form of anaemia has been noticed by Houston'* in mel- 
ancholia and general paralysis, and by Smith^ in various forms of 
insanity. 

Krypiakiewicz* noticed an increase of eosinophils in acute 
forms of insanity but not in the chronic forms. The leucocyto- 
sis of acute deliriimr' is exemplified by the following case from 
the Massachusetts Hospital records : 

J Miinch. med. Woch. , 1895, No. 14. 

2 Houston : Boston Med. and Surg. Journal, January 11th, 18^4. 

3 Smith : Jour, of Ment. Sc. , October, 1890. 

* Krypiakiewicz : Wien. med. Woch., 1893, No. 25. 
^ Ref . in Klein-Volkmann's "Sammlung klin. Vortrage," December, 
1893. 



274 



SPECIAL PATHOLOGY OF THE BLOOD. 



A girl of fifteen; acute delirium; leucocytes, 12,750; no food 
for eight hours ; red cells, 4,510,000; haemoglobin, 63 per cent. 

Puerperal mania is to be distinguished from the delirium of 
puerperal sepsis by the fact that the latter shows leucocytosis 
with increased percentage of adult cells, while the former has 
no leucocytosis (if uncomplicated) and the eosinophils are apt 
to be increased ' (diminished in sepsis) . 

A case of puerperal mania seen by the writer showed : Eed 
cells, 5,210,000; white cells, 6,500; haemoglobin, 84 per cent; 
eosinophiles, 8 per cent. 

CONSTITUTIONAL DISEASES. 
OBESITY. 

Oertel distinguishes a plethoric and an anaemic form of 
obesity not merely clinically' but by the evidence of post-mortem 
examinations. He believes that there is a real over-filling of 
the vessels in the first. The second form occurs most often in 
women. 

Kiscli examined (with v. Fleischl's instrument) the haemo- 
globin of 100 obese patients; 79 showed over 100 per cent of 
haemoglobin, 1 reaching 120 per cent, while the other 21 were 
anaemic. 

DIABETES. 

There is nothing characteristic about the blood except the in- 
creased amount of sugar to be detected (.57 per cent as against .1 
normally) ; but this is not a clinically applicable test. 

The alkalinity has been said to be greatly diminished, espe- 
cially in the fatal coma, but v. Noorden thinks the tests are un- 
reliable. 

Fat is often much increased in the blood, so that the serum is 
milky, and glycogen has been demonstrated microchemically in 
the corpuscles. 

Bed Cells. 

Sugar in the blood draws water from the tissues into the 
vessels, thereby diluting the blood: but in a short time the blood 

^ Neusser : Loc. cit. 



GOUT. 



275 



frees itself of tlie excess of sugar and fluid through increased 
diuresis so as to concentrate the blood. 

These two alternating influences serve to explain the widely 
difi'erent counts of different observers. 

Toward the end of the disease a decided cachexia often de- 
velops, the anaemia of which may be temporarily covered up by 
the concentration above noted, or accentuated by the dilution 
which sometimes occurs. Accordingly we may find the corpus- 
cles increased, normal, or diminished in different cases or at 
different times with the same case. 

Grawitz counted 4,900,000 red cells in a patient in compara- 
tively good health, and three weeks later, when the patient had 
just been seized with the fatal coma, the count showed 6,400,000 
per cubic millimetre. 

The white cells show no constant changes, except that v. 
Limbeck has noted in several cases that the digestion-leucocy- 
tosis is unusually large even without previous fasting. Yon 
Jaksch found leucocytosis in one of his eight cases, but on this 
point as on many others his results are almost unique. The 
only similar observation is that of Habershon, ' who reports 
moderate leucocytosis, decreased by strict diet. 

GOUT. 

A few cubic centimetres of serum from gouty blood made acid 
with acetic acid (six drops of a twenty -eight-per-cent solution 
to every drachm of serum) deposit crystals of uric acid on a 
thread in from eighteen to forty-eight hours ; but this is not al- 
ways to be found, and is by no means peculiar to gout."^ Uric 
acid is to be found in the blood in pneumonia, cirrhotic liver, 
nephritis, grave anaemia, leukaemia, and gravel ; also in health 
and after a meal of calf's thymus or any food containing much 
nuclein. 

The red corpuscles show no special changes except in severe 
chronic cases which are sometimes anaemic. The white cells are 
increased according to Neusser, while v. Limbeck and Grawitz 
found the blood wholly normal. 

1 St. Bartholomew Hosp. Rep., 1890, p. 153. 

2 It is important to evaporate the serum at a temperature not above 70° 
F. , otherwise crystals will not form. 



276 



SPECIAL PATHOLOGY OF THE BLOOD. 



It is particularly in this disease that Neusser finds the peri- 
nuclear basophilic graDulations in the white cells, which he be- 
lieves to be characteristic of any "uric-acid diathesis." Fibrin 
is increased in acute cases. 

MYXCEDEMA. 

Le Breton^ examined the blood in one case before and after 
thyroid treatment and found after forty days' treatment that the 
red cells had risen from 1,750,000 to 2,450,000, the white from 
4,500 to 9,600, and the haemoglobin from 65 to 68 per cent. 

The remarkably high color index in this case before treat- 
ment (nearly 2. !) corresponds with the observations of Le Breton 
in the dried specimen, which showed a decided increase in the 
size of the red corpuscles. He also noticed before instituting 
the thyroid treatment the presence of nucleated red cells and 
an excess of the adult form of leucocytes. Under treatment the 
nucleated red cells disappeared and the young forms of leuco- 
cytes rose to their normal per cent. 

Putnam^ has watched a similar case in which the red cells 
rose from 3,120,000 to 5,700,000 under thyroid treatment. 

Murray^ has collected 23 cases with blood examinations. Of 
these 7 showed normal blood, 10 were anaemic, 4 had leucocyto- 
sis, and 2 had both anaemia and leucocytosis. 

Kraepelin'' noticed (like Le Breton) a marked increase in the 
average diameter of the corpuscles in three cases, even when the 
count and the lisemoglobin were normal. 

I have had an opportunity to examine the blood in three 
cases of this disease, but did not find anything remarkable in 
any of them. 



Case. 


Red cells. 


White cells. 


Per cent 
Haemoglobin. 


1 


4,670,000 
4,460,000 
4,856,000 


6,000 
8,800 
5,200 


87 


2 


3 


80 





^ Le Breton : Ref. in Wien. med. Blatter, 1895, p. 49. 

2 Putnam : Ref. in Murray's article in "Twentieth Century Practice of 
Medicine," vol. iv. 

3 Murray: "Twentieth Century Practice of Medicine," vol. iv., p. 710. 
^ Kraepelin : Deut. Arch. f. klin. Med., vol. xlix. , p. 587. 



Addison's disease. 



277 



Differential counts were made in three cases and no increase 
in tlie size of the corpuscles, such as Le Breton and Kraepelin 
saw, was present in these cases. The count showed: 



Case. 


Adult cells. 


Young cells. 


Eo&inophiles. 


1 




67 


28 


5 


2 




67 


27.8 


4.4 


3 




74 


26 





The increase of eosinophils in two of these cases may per- 
haps be due to the skin troubles present in the disease. 

J. J. Thomas found a few myelocytes in a case of Putnam's. 



GRAVES' DISEASE (BASEDOW'S DISEASE; EXOPHTHALMIC 

GOITRE). 

The blood is normal, except for an occasional associated 
chlorosis and sometimes a marked lymphocytosis. In one case 
I found 51.3 per cent of young cells and 1 per cent of myelocytes 
in 1,000 leucocytes, the adult cells being only 48 per cent; but 
in fourteen other cases I have never found this again. The 
same fact has been noticed by Neusser (cited in Klein, loc. cit.). 

Oppenheimer' found the red cells and haemoglobin normal in 
two cases. Yon Jaksch' in one case " complicated with myx- 
cedema" found 3,818,000 red and 8,000 white cells. 

The association of Graves' disease with chlorosis is illus- 
trated by two cases from Zappert :^ 



Case. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


1 


2,858,000 
2,738,000 


3,800 
3,800 


32 
30 


2 





The same writer found eosinophiles much increased (8.5 per 
cent) in one out of four cases. 



ADDISON'S DISEASE. 

Some, but not all, cases are accompanied by marked anaemia. 
Neumann" observed a case in which the symptoms came on 

1 Deut. med. Woch., 1889, p. 861. 

2 Zeit. f. klin. Med., 1893, p. 187. 

3 Zeit. f . klin. Med. , 1893, p. 266. 

4 Neumann : Deut. med. Woch., 1894, p. 105. 



278 



SPECIAL PATHOLOGY OF THE BLOOD. 



acutely and the red cells sank to 1,120,000 per cubic millimetre. 
During the convalescence which followed the cells ran up above 
normal, reaching 7,700,000. 

Tschirkoff ' reports two cases in which the red cells were re- 
spectively 3,280,000 and 2,933,000 at the lowest, but whose 
haemoglobin was extraordinarily high, over 100 per cent in one 
case. This he found on spectroscopic examination to be due to 
a great increase of reduced haemoglobin in the corpuscles. 
Methaemoglobin was also noted. 

The white corpuscles showed no changes, quantitative or 
qualitative, except that they contained black pigment granules. 
Two cases have been examined at the Massachusetts Hospital. 
The first, a woman of thirty, showed 6,240,000 red cells with 14,- 
000 white, and 90 per cent of haemoglobin. The differential 
count of 900 leucocytes showed the following figures: Adult 
cells, 53.4 per cent; young cells, 41 per cent; eosinophils, 4.5 
per cent; myelocytes, .9 per cent. 

The eosinophiles were very large, some of them eosinophilic 
myelocytes. 

The second case was very anaemic and weak at entrance and 
showed the following condition: Red cells, 2,196,000; white 
cells, 7,500; haemoglobin, 20 per cent. Differential count of 
200 leucocytes showed: Adult cells, 65 per cent; young cells, 
31.5 per cent; eosinophiles, 3.5 per cent.; five normoblasts; 
marked poikylocytosis. 

Under suprarenal extract his blood improved in a month till 
his red cells numbered 4,700,000, white cells, 9,000; haemoglo- 
bin, 65 per cent. 

A third patient, kindly sent me by Dr. Rogers, of Dorchester, 
showed: Red cells, 2,864,000; white cells, 2,000; haemoglobin, 
51 per cent. Differential count of 300 cells showed: Adult 
cells, 63.3 per cent; young cells, 33.3 per cent; eosinophiles, 
2.3 per cent; basophiles, .3 per cent. 

I have never seen melanin in the leucocytes as Tschirkoff 
did in his two cases, 

OSTEOMALACIA. 

The blood has for a long time been supposed, on the author- 
ity of V. Jaksch (Zeit. f. Min. Med., Vol. 13, page 360), to exhibit 
1 Zeit. f. klin. Med., 1891, vol. xix., Suppl. Heft 37. 



RICKETS. 



279 



a diminished alkalinity, the bones being supposed to be eaten 
away by acids in the blood. Yon Limbeck and many other ob- 
servers have lately shown that the blood is normal in alka- 
lescence. 

Corpuscles and haemoglobin are usually within normal limits 
quantitatively, but Neusser reports an increase of eosinophiles 
and the presence of myelocytes in the blood. 

Eitchie' confirms Neusser and found also the young leu- 
cocytes more numerous than normal. 

Fehling," Sternberg," Chrobak' found no increase of eosino- 
philes. 

Eieder's case was normal in all respects: Eed cells, 
4,892,000; white cells, 5,600; eosinophiles, 3.6 percent; adult 
cells, 61 per cent. 

RICKETS. 

1. Anaemia is always present in severe cases and often in 
moderate ones. This, together with the fact that many cases 
of rickets are associated with an enlargement of the spleen, has 
led to the use of the misleading term "splenic anaemia." 

Hock and Schlesinger found an average of 2,500,000 red cells 
in a considerable number of cases with and without enlarged 
spleen. 

Von Jaksch describes a case in which the red cells sank from 
1,600,000 to 750,000 within three months, and Luzet saw a simi- 
larly rapid process, the cells falling from 2,110,000 to 1,596,- 
000 within three weeks. 

2. Apparently the haemoglobin per corpuscle is normal — that 
is, the color index is not low. Monti and Berggriin found 
40-50 per cent haemoglobin with 3,148,000 red cells and Hock 
and Schlesinger 60 per cent haemoglobin with 2,300,000 cells. 

White Goiytisdes. 

It is often difficult to say whether or not the leucocytes are 
increased, owing to the occurrence of most cases in infants at an 
age when leucocytes are always higher than in adults — how 
much higher at any given age depends largely upon the degree of 

* Edin. Med. Journal, June, 1896. 
2 Cited by Ritchie {loc. cit) . 



280 



SPECIAL PATHOLOGY OF THE BLOOD. 



vigor and forwardness of development of tlie individual child. 
At any rate, tlie counts are usually from 15,000 to 40,000 with 
considerable variations from week to week. 

Qualitative Changes. 
Red Cells. 

As in all anaemias of infants, the "degenerative" and "re- 
generative" changes are relatively common. 

Polychromatophilic forms and nucleated corpuscles are fre- 
quently to be found, the latter often in great numbers but with a 
majority of the normoblast type. 

White Cells. 

Lymphocytosis is marked, but, as with the question of leu- 
cocytosis, we are never quite sure whether the numbers are ab- 
normal for that age, for lymphocytosis is the normal condition in 
infants' blood. 

'WTien, however, as in a case mentioned by Rieder, we find 
75 young cells in every 100 leucocytes, the child being four 
years old, we are surely dealing with a pathological condition. 
Another of his cases, a seven-months' child, rachitic, with 
57 per cent of young leucocytes, seems to fall within normal 
limits. The same difficulty arises with regard to the reports of 
eosinopJiilia in rickets, since eosinophils are always relatively 
numerous in infancy. In Eieder's four cases and in the three 
seen at the Massachusetts Hospital, no eosinophilia was pres- 
ent. Myelocytes in small number (.5-2. per cent) are not un- 
common, and may be considerably more numerous. 



CHAPTEE IX. 



BLOOD DESTRUCTION AND HEMORRHAGIC DIS- 
EASES. 

1. PURPURA HEMORRHAGICA. 

The blood is practically that of ansemia from hemorrliage 
(red cells and haemoglobin reduced, white cells increased, occa- 
sional nucleated red corpuscles or polychromatophilic forms). 
Agello ^ has found methsemoglobin in the blood, and hence con- 
cludes that the disease is a poisoning of the corpuscles by 
ptomains absorbed from the intestine. 

The blood plates are much diminished and may be entirely 
absent in the worst stages. 

Bacteria of various kinds have been reported in the disease, 
but negative results are also common, and their presence is 
probably not significant. 

The red cells may fall as low as 2,500,000, but are much 
oftener slightly or not at all diminished. In many mild cases- 
there are no demonstrable blood changes. On the other hand^ 
Osier mentions a case which sank to 1,800,000. 

SCURVY. 

There are no characteristic blood changes known. When 
hemorrhage is severe the red cells may sink very low, to 557,875 
in a case of Bouchut's; Ouskow and Hayem saw counts of 
3,500,000 and 4,700,000. The usual qualitative changes of sec- 
ondary anaemia are present in severe cases; haemoglobin suf- 
fers as usual more than the count of red cells. 

Leucocytes are generally increased, whether from hemor- 
rhage or from some complicating inflammatory process. 

Barlow's disease may lower the red cells as far as 976,000 — 

1 Riforma Med., Napoli, 1894, p. 103. 

19 



282 



SPECIAL PATHOLOGY OF THE BLOOD. 



as in a case of Eeinert's — the haemoglobin being seventeen per 
cent and the white cells 12,000. This was the day before death. 



HEMOPHILIA. 

The blood changes are practically those just described and 
show nothing characteristic of the disease. Coagulation is 
slower than normal and blood plates are sometimes very scanty. 



BLOOD DESTRUCTION (HEMOCYTOLYSIS) . 

I. Besides the slow destruction of corpuscles which takes 
place in any ordinary anaemia, we have a group of conditions 
under which a large number of red cells are suddenly destroyed 
in the circulation itself. This may take place by — 

1. Separation of the haemoglobin from the corpuscles so that 
it colors the serum. 

2. Actual breaking to pieces of the red cells without separa- 
tion of the haemoglobin. 

If normal blood is drawn and left to stand, the serum which 
separates from the corpuscles is not red-tinged or but very 
slightly so, lorovided all shaking and jarring are avoided. A very 
slight reddish tinge may appear in the serum even with most 
careful technique. In some conditions the haemoglobin, while 
not actually separated from the corpuscles within the vessels, is 
so loosely connected to them that a considerable quantity sepa- 
rates post mortem and colors the serum in spite of the avoid- 
ance of any jar. 

This condition is to be distinguished from true haemoglobin- 
semia, in which the serum is actually colored before leaving the 
Tessels, although the two conditions really represent only dif- 
ferent degrees of vulnerability of the red cells. 

We are surer of a diagnosis of hfemoglobinaemia when we find 
bits of broken-down cells in the fresh blood and the additional 
-evidence of haemoglobinuria or jaundice. 

1. Severe forms of malaria, yellow fever, typhus fever, 
severe forms of septicaemia, and rarely scarlet fever may cause 
iiaemoglobinaemia. 

2. Paroxysmal hcemoglobinmnia, so-called, is a varietj^ whose 
cause is unknown and which does not seem secondary to any 



BLOOD DESTRUCTION (H^MOCYTOLYSIS). 283 

other disease, unless a certain relationship to syphilis be es- 
tablished, and possibly to malaria. The attacks are brought on 
by a great variety of causes (cold, muscular or mental strain, 
etc.)- Some persons can always bring on an attack by putting 
the hand or foot into cold water. 

Blood Examination. 

Coagulation is very rapid, but the clot soon dissolves again 
(Hay em). The fresh blood shows deformities in the corpuscles 
and bits of broken cells, if examined during a paroxysm. The 
following figures from Grawitz illustrate the loss of cells from a 
single paroxysm. Before the paroxysm: Red cells, 4,750,000; 
white cells, 12,000. Toward the end of the paroxysm: Red 
cells, 3,620,000; white cells, 12,000. 

Haemoglobin is decreased equally with the red cells. The 
loss is soon made up again in most cases, and between the par- 
oxysms we may find normal blood or only a slight anaemia. 
The leucocytes are normal. 

The serum is brilliantly red-colored at the time of the par- 
oxysm. 

All that is known of the disease is expressed by saying that 
for some reason the red cells are abnormally sensitive, so that any 
one of a variety of slight disturbances is sufficient to separate 
their haemoglobin and set it loose in the plasma. 

3. Extensive hums have been reported to cause haemoglo- 
binaemia with breaking up of the red cells, presumably through 
changes in the serum similar to those which make duodenal 
ulcer so common a sequel to bad burns. 

4. Snake poison and scorpion poison may have similar 
effects. 

11. Another group of corpuscle destroyers is that which 
works by changing the hcemoglohin to m,ethcemoglobin. The 
most important of these is — 

1. Glilorate of Potash. — This destroys the corpuscles and pro- 
duces haemoglobinaemia and the usual train of symptoms (jaun- 
dice, dark urine, etc.) due to this. 

Brandenburg' examined the blood of a woman who had taken 
two and one-half ounces of chlorate of potash in water the night 
before. The blood showed marhed leucocytosis, broken and 
> Berliner klin. Woch., 1895, No. 27. 



284 



SPECIAL PATHOLOGY OF THE BLOOD. 



distorted red cells. In gross it was chocolate-colored and the 
serum after separation of the clot was brown. The red cells 
progressively decreased as follows : 



Red cells. White cells, 

First day 4,300,000 20,000 

Second day 2,500,000 

Fourth day 2,300,000 

Fifth day 2,100,000 

Sixth day 1,900,000 

Seventh day 1,600,000 15,000 (death). 



2. Antipyrin and antifehrin in doses of thirty to forty -five 
grains may cause great cyanosis and dangerous prostration 
through transformation of the haemoglobin and methaemoglobin. 
In certain persons much smaller doses produce the same effect. 

3. Phenacetin looisoning (Kronig: Berl. Min. Woch., 1895) 
may cause actual blood destruction with anaemia in case the 
patient survives the immediate effects of the deprivation of 
oxygen. 

4. FJiosphoTus looisoning (see Liver, page 251). 

5. Workers in aniline dyes and nitroglycerin factories may 
be severely poisoned by nitrohemol compounds inhaled and pro- 
ducing methaemoglobinaemia. 

6. PyrogalUc acid and pyrogallol as used in treatment of skin 
diseases may lead to death through destruction of the red cells. 
Chromic acid (for instance, as applied through the vagina) may 
have a similar effect. 

Many other less common substances work the same ill-effects 
on the blood. 

III. A third group of substances, of which carhonic oxide gas 
is the type, poison by combining chemically with the haemo- 
globin and preventing its combination with the oxygen of the 
air. 

1. Illuminating gas is for our purposes the most important 
of this group, with carbonic oxide gas second. 

The appearance of individual blood cells is not altered nor 
do they break up, but the corpuscles are useless to breathe with, 
as they cannot take up oxygen. 

The color of the blood is very bright red, much brighter than 
normal. 



BLOOD DESTRUCTION (H^MOCYTOLYSIS) . 285 



Red Cells. 

Von Limbeck' found in two cases 6,630,000 and 5,700,000 
respectively. The volume of these corpuscles (estimated by 
Bleibtreu's method) was greatly increased, amounting to 70.7 
per cent (normal 41-48 per cent) , so that apparently the size of 
the individual cells is increased. 

Miinzer and Palma^ found 5,700,000 red cells in one case. 

Leucocytes. 

Eaton^ reported four cases, in all of which the white cells 
were increased, the counts ranging between 15,000 and 22,000 
per cubic millimetre. 

Miinzer and Palma {loc. cit.) found 13,300 in their case. 
Two such cases have been examined at the Massachusetts Hos- 
pital with the following results : 



Case. 


Red cells. 


White cells. 


Remarks. 


1 


4,930,000 


17,500 
21,200 
15,500 




2 


November 27th, comatose. 
November 29th, convalescent. 







Warthen* reports the same condition in a single case. Here 
the specific gravity was also very high (v. Limbeck finds that 
this is to be explained by the increase in the actual size of the 
corpuscles) . 

When there is any doubt as to diagnosis, the following test 
will settle it : Shake a small quantity of fresh-drawn blood into 
three times its volume of subacetate of lead. If the blood con- 
tains CO the mixture becomes of a fine red color; otherwise it 
turns chocolate-colored.^ 

2. Da Costa {31ed. News, March 2, 1895) reported a consider- 

J Loc. cit. , p. 234. 

2 Zeit. f. Heilk., vol. xv., p. 1. 

^ Boston Medical and Surgical Journal, March 14th, 1895. 

^ Virchow's Archiv, vol. cxxxvi. 

^ Rubner : Zeit. f. anal. Chemie, xxx., p. 112. 



286 



SPECIAL PATHOLOGY OF THE BLOOD. 



able diminution in haemoglobin of patients during etherization^ 
especially anaemic patients, but the investigations of Lerber ' do 
not confirm this. 

Tansy Poisoning. — A single case examined at the Massa- 
chusetts General Hospital showed: Ked cells, 4,600,000; white 
cells, 21,000 ; haemoglobin, 70 per cent. 

Inaug. Dissert., Basel, 1896. 



PART VI. 



MALIGNANT DISEASE, BLOOD PARASITES^ 
AND INTESTINAL PARASITES. 



CHAPTEE X. 
MALIGNANT DISEASE. 

The Blood as a Whole. 

1. The specific gravity is reduced in most cases, running 
roughly parallel with the haemoglobin. 

2. Coagulation is normal or slower than normal in uncom- 
plicated cases. When sloughing and inflammation are present 
it may be rapid. 

3. Fibrin is usually normal; an increase means inflammation 
in or around the tumor or an inflammatory complication. 

CANCER. 
Red Corpuscles. 

As in tuberculosis, we are frequently surprised to find but 
little diminution in the number of red cells. In all but very ad- 
vanced cases this is the rule. It is a change of the individual 
red cells (pallor, loss of size, of weight, degenerative changes), 
rather than a reduction of numbers. 

Nevertheless in the later cachectic stages of most cases of 
malignant disease, we do find a quantitative anaemia, the counts 
often running as low as 2,500,000 and occasionally sinking as 
low as in pernicious anaemia. Thus v. Limbeck records a case 
(complicated by repeated hemorrhages) with only 950,000 red 
cells per cubic millimetre. The lowest of my own cases was. 
1,632,000 per cubic millimetre. 



288 



SPECIAL PATHOLOGY OF THE BLOOD. 



There seems to be no considerable difference between cancer 
and sarcoma as regards their effect on the red cells. 



Table XXXIX., A.— Gastric Cancer Without Leucocytosis. 



c 


Age. 


Sex. 1 


Red 
cells. 


Wliite 
cells. 


Per cent 
hsemo- 
globin. 


Remarks. 


— 
1 




42 


M. 




6,040,000 


4,400 


48 










7,200 




One week later; mealtime, April 14th. 










8.900 




Four hours after meal. 










5.140 




April 16th, mealtime. 










4,400 




April 16th, three and one-half hours later. 










6.500 




April 17th, mealtime. 










6.0.58 




April 17th, three hours after. 




59 


M. 


3,900,000 


5.000 




3 


71 


F. 


5,880,000 


4.800 


90 




4 


63 


M. 


3,470,000 


5.000 






5 


71 


M. 


3,744,000 


5,200 






6 


54 


F. 


4.772,000 


5,600 






7 


63 


M. 


5,040.000 


6.000 




Operated. 


8 


54 


M. 


5,200.000 


6.000 


42 


9 


52 


M. 


3,200,000 


5.200 


25 


Operated. 


10 


34 


M. 


2,296,000 


6.150 


27 


July 28th, 1895, before eating. 








5,650 




July 28th, 1895, three and one-half hours after 














eating. 










10,600 




July 20th. In 500 white cells: poljTiiorphonu- 














clear, 78 per cent: small lymphocytes, 13; 














large lymphocytes, 9. No nucleated red cells. 


11 


Adult. 


F. 


1,940,000 


6,660 


26 


December 12th, 1895. 








1,947,000 


8.000 


22 


January 8th, 1895. 


12 


Adult. 


M. 


4,612,000 


6,300 


70 


13 


52 


F. 


3,680,000 


6,-327 


33 


No nucleated red cells. Slight poikylocytosis. 


14 


43 


M. 


5,472,000 


6,500 


78 








6,527 




Ten days later, mealtime. 










5..306 




Ten days later, four hours after meal. 










10,180 




Eleyen days later, mealtime. 










8. 886 




Eleyen days later, four hours after meal. 


15 


39 


M. 


5,000,000 


6.500 


80 


Considerable dilatation. 


16 


34 


F. 


5,480,000 


7.000 


75 


Noyember l8th, 1895. Considerable dilatation. 








4..500 




December 2d. 1895, before meal. 










8,000 




December 2d, 1895, four hours after meal. 


17 


47 


M. 


3,168,000 


7,300 


38 


18 


68 


M. 


4,880,000 


7,600 






19 


33 


M. 


3,200,000 


8.000 






20 


Adult. 


M. 


4,632,000 


8.400 


45 


Autopsy. 


21 


52 


F. 


6,928,000 


8.600 


78 


In 1.000 white cells: 62.5 per cent polymorpho- 














nuclear; 21 small lymphocytes; 15.5 large 














lymphocytes: 1 eosinophiles. Autopsy, one 














month later. 


22 


48 


M. 


3,708,000 


8.750 


43 












13.225 




One month later, before meal. 


23 








12.175 




One month later, four hours after meal. 


51 


M. 


3,860,000 


9,250 


58 


December 26th. 










11.370 




January 10th. 1 : 30 p.m. 










12,100 




January 10th, 5 p.m. 


24 


66 


M. 


3,704,000 


9,391 


50 


25 


Adult. 


M 




9,600 




400 white cells show polymorphonuclear, 62 per 










cent; small lymphocytes. 24; large lympho- 


26 




M. 








cytes, 10; eosinophUes. 4. 


40 


4,460,000 


9.750 


60 


27 


56 


M. 




9.330 




Four hours after meal. 


2,928,000 


9,800 


35 


September 27th. Haemoglobin: August 21st. 














44 per cent. ; September 1st, 46; September 


28 












6th, 52. 


Adult. 


F. 


2,400,000 


10.000 




29 


Adult. 


M. 


5,120.000 


10.500 


86 




30 


44 


M. 


2,984,000 


10.600 


25 





CANCER. 



289 



Table XXXIX., B. — Gastric Cancer with Leucocytosis. 



Age. 



65 

61 

53 
Adult. 
Adult. 
Adult. 

56 

46 

41 

59 



50 



Red 
cells. 



4,280.000 
3,680,000 
5,992,000 
6,296,000 
5,512,000 
5,152,000 



4.640,000 
4,150,000 
4,240,000 

3,928,000 
3,160,000 
2,256,000 



4,-308,000 



2,516,000 

1,632,000 
4,700,000 
3,800,000 
4,700,000 
5,900.000 
5,400,000 



White 
cells. 



11,000 
12,000 
12,000 
12,000 
12,400 
12,400 
14,700 
15,000 
16,800 
19,200 

14,800 
15,200 
27,000 



16,300 
15,950 
14,170 
10,000 



10,300 
40,000 

15,950 
19,142 
19,800 
32,500 
36,400 
39,000 



Per cent 
hsemo- 
globln. 



25 



70 



30 



50 



Remarks. 



Differential couTit: Poly., 

cytes, 16 ; eosinophile, 4. 
October 17th. 
October 27th. 

Differential count: Poly., ! 
cytes, 3; eosinophiles, 1 ; 



30 per cent; lympho- 
September30th, 1895. 



'6 per cent ; lympho- 
normoblasts, 2 ; me- 
galoblasts, 2. Died February 24th, 1896. Au- 
topsy. 
November 25th, 1895. 
December 3d, before proteid meal. 
December 3d, three hours later. 
December 19th. Differential count of 300 cells: 
Poly., 75.7 per cent; small lymphocytes, 18.7; 
large lymphocytes, 4.3; eosinophiles, 1.3. 
January 8, 1896. 

April 1.3th, 1896. Differential count of 300 cells: 

Poly., 86.5 percent; lymphocytes, 13.5. 
April 26th. Died May 1st. Autopsy. 
Supposed pernicious anaemia. 



One week later. 



As will be seen by consulting Tables XXXIX., A, B, the 
count of red Cells is sometimes above normal, doubtless due to 
concentration of the blood from some cause. Probably the same 
influence is at work in other cases, and many of those showing 
normal counts have really fewer red cells than they should. Such 
abnormally high counts are not rare, as the following examples 
show : 



Author. 


Case. 


Osterspey ^ . . 


1 


Osterspey 


3 


Osterspey 


3 


Neubert ^ 


1 




2 







Affection. 



Cancer of the stomach 

Cancer of the liver and stomach 

Cancer of the gullet 

Cancer of the stomach 

Cancer of the liver 

Cancer of the stomach 



Red cells. 



5,040,000 
6,184,000 
8,280,000 
5,085,000 
4,918,000 
6,200,000 



• Dissert. , Berlin, 1892. 

2Inaug. Dissert., Dorpat, 1889. 

3 "Zahlung d. Blutkorp.," Leipzig, 1891. 



290 



SPECIAL PATHOLOGY OF THE BLOOD. 



I wish to lav some stress upon this point, because it has been 
stated by some recent writers {e.g., Grawitz: "Pathologie des 
Bhites," Berlin, 1896) that the red cells are almost always dim- 
inished in malignant disease. 

The high counts in cancer of the gnllet are obvionsly to be 
explained by the lack of licxuid taken, the blood being greatly 
concentrated as in any other form of starvation. 

That this increase is not invariably present (see Table XL., 
page 300) is doubtless because some oesophageal tumors permit 
the ingestion of liquid in normal amounts and of a certain 
amount of solids. 

The highest counts in the Massachusetts Hospital series are 
in simple gastric cancer without any stenosis at either end of the 
organs (see Cases I., III., XA^T., and XXL), and the lowest 
count (1,632,000) was in a similar case just before death. Tak- 
ing all the cases of cancer in this series together, tlie average of 
the severity -five cases at the time when treatment began ivas 4,140,- 
000 red cells per cubic millimetre. 

Hcemoglolrirt. 

Bierfreund/ who has examined seventy-two cases with re- 
gard to their percentage of coloring matter, found that in rela- 
tively slow and long-standing cases it averaged 68.5 per cent, 
and in the worst cases 57.5 per cent. After the operation the 
haemoglobin, is of course lower owing to hemorrhage, and Bier- 
freund noticed that as a rule the haemoglobin began to rise 
toward normal much later than after operations for non-malig- 
nant conditions — a week later on the average — and that it never 
reached the j^oint at ivhich it ivas before the operation.' 

The following table from Bierfreund is of interest as 
illustrating these points. Cases were examined before and 
after operation, and the examinations were continued daily 
after the operation until the hsemoglobin began to rise 

' Langenbeck's Archiv, vol. sli. 

' This is all the more extraordinary because Bierfreund specially noted 
that even in patients who gained weight notably after the operation the 
heemoglobin did not rise so high as it had been before operation ; he 
watched thera for months after it. Apparently the actual presence of 
the tumors is not the only cause of the lack of corpuscle substance. 



CANCER. 291 



again. This occurred very late as compared with other 
operations. 



Diagnosis. 


Per cent 
heemoglobin 
before 
operation. 


Per cent 
haemoglobin 
after 
operation. 


Per cent 
loss. 


Regeneration time. 


Malignant tumor without 
complication. 

Very large or rapidly grow- 
ing tumors. 

Tumors with "softening" or 
disturbances of function. 


68.5 
56.6 
57.5 


53 

38.4 

39.7 


15.5 
18.2 
17.8 


23 days. 
27.8 days. 
27 days. 


Total, 72 cases. 


Av. , 60 


Av., 42.8 


17.2 


Av., 25.9 days. 



By "regeneration time" is meant the number of days 
elapsed after operation before the haemoglobin hegms to rise. 
After operations for other causes (non-malignant) the average 
regeneration time is fourteen to twenty days. 

It is very important that these results of Bierfreund's should 
be tested. In Mikulicz's surgical clinic at Breslau all patients 
have their haemoglobin tested regularly. In this country the 
surgical portion of the profession have not as yet taken hold of 
blood examination, and many questions about the blood in sur- 
gical affections remain unanswered. 

Eeinbach' examined 16 cases and found the haemoglobin range 
between 18 to 70 per cent, with an average of 50 per cent. 

Kieder's^ cases average 53 per cent (sarcoma much lower — 
see below) . 

Laker'' noticed the low haemoglobin percentage in malignant 
tumors and thought it a help in excluding benign tumors or 
tuberculosis, in which the haemoglobin is much less diminished. 

In the 48 cases of malignant tumors in which I have notes of 
the haemoglobin (see tables) the average is 54 per cent. Com- 
paring this with the average count of red cells (4,140,000), we 
get a color index of .65, distinctly higher than the average of 
chlorotic cases, of which, however, the figures distinctly remind 
us. The highest cases of this series had 100 per cent and 90 
per cent of haemoglobin respectively, and the lowest 20 per cent 



^ Langenbeck's Archiv, 1893, p. 486. 

2 "Beitrage z. Kenntniss d. Leucocytosis," Leipzig, 1892 (Vogel). 

3 Wien. med. Woch., 1886, Nos. 18 and 19. 



292 



SPECIAL PATHOLOGY OF THE BLOOD. 



and 22 per cent ; in these last two cases the color indexes were 
.36 and .58 respectively, not excessively low. 

As the disease progresses, the red cells and haemoglobin 
steadily go down (except in cancer of the gullet), and at the time 
of death 1,000,000 cells i)er cubic millimetre is not rare. 

The color index always remains below 1. Compared to most 
other varieties of secondary- anaemia {e.g., those in tuberculosis 
or nephritis) a quantitative anaemia — that is, a loss of red cells 
as well as of haemoglobin — is relatively more frequent. In gen- 
eral the degree of anaemia is parallel to the amount of cachexia, 
except when hemorrhage increases it (as in tumors of the stom- 
ach or uterus). 

How far the anaemia msbj be due to actual destruction of cells 
by toxic (?) products of the tumors is doubtful. Grawitz found 
that the injection of extracts of cancerous tissues caused in 
rabbits a temporary dilution of the blood, so that the cells per 
cubic millimetre were diminished, and it may be that this plays 
some part in the causation of the low blood counts. 

Qualitative Changes. 

(a) The average diameter of the red cells is often diminished 
either (as in chlorosis) by a diminution of the size of nearly 
every corpuscle, or by a less general shrinkage, many cells being 
of normal size. The very large forms seen in pernicious anaemia 
are rare in the anaemia of malignant disease, and never, I think, 
reach the size of the giant forms seen in the former condition. 
Very small cells, on the other hand, are as common in ad- 
vanced cases as in anj^ other form of anaemia, except chlorosis. 
Deformities and degenerative changes are very common in well- 
marked cases. 

According to Strauer, the deformities found in malignant 
disease are greater than those found in any form of tuberculosis, 
and this fact he thinks of value in diagnosis. 

Degenerative changes are often w^ell marked, but seldom, if 
ever, reach so extreme a condition as occurs in many cases of 
pernicious anaemia. 

(J)) Nucleated red corpuscles are the rule in all advanced cases, 
and in some that are not advanced. Malignant disease differs 
in this respect from tuberculosis and most other conditions in- 
volving secondary anaemia, in that the nucleated red cells may 



CANCER. 



293 



appear even when there is no considerable loss of red cells 
(numerically) or even when the haemoglobin is also normal 
(Schreiber) . 

As a rule the nucleated corpuscles are of the normoblast 
types (including small forms with dividing nuclei), but in very 
cachectic cases we may find megaloblasts as well — always, so far 
as I know, fewer in number than the normoblasts. This consti- 
tutes one of the points of distinction between pernicious anaemia 
and the severest types of secondarj^ anaemia, such as occur in 
malignant disease. The megaloblasts, when present, are in the 
minority as compared with the normoblasts. 

The characteristics of the blood changes in malignant disease, 
then, so far as concerns the red cells, are those of secondary 
anaemia, which at times attains the severest type — but only 
w^hen cachexia is marked, or when hemorrhage complicates the 
disease. 

The specific gravity follows in a general way the haemoglobin 
percentage. 

On the lohite corpuscles in malignant disease a great deal of 
interest has centred, and very conflicting reports have been 
published. As the effects of cancer and sarcoma seem to be 
somewhat different we will consider them separately. 

1. The Leucocytes in Cancee. 
(a) Quantitative Changes. 

We should expect great differences in the blood of different 
cases if we consider what a wide range is included between the 
small, hard, slow-growing, curable cancer of the lip which may 
produce little or no impairment of the general health, and the 
"fulminating," rapidly growing cases with numerous metastases 
and profound prostration. 

The former class of cases may show a blood normal in all 
respects, including a normal leucocyte count ; while in the latter 
the blood may be so profoundly altered as to be confused with 
that of pernicious anaemia on the one hand, or with that of leu- 
kaemia on the other. 

In a general w^ay it may be said that the. more "malignant" 
the cases the greater the changes in the blood. 



294 



SPECIAL PATHOLOGY OF THE BLOOD. 



The effect upon the leucocytes depends upon the following 
conditions : 

1. The position of the tumor. 

2. Its size, rapidity of growth, and the number, size, and 
position of its metastases. 

3. The resisting power of the individual. 

1. Position. — {a) Tumors of the gullet involving stricture but 
not extending to other tissues are often accompanied by a dim- 
inution of the leucocyte count, owing to the starvation which 
they produce. This is not true of all cases, as is shown in the 
accompanying tables, but when the leucocytes are increased there 
is usually an involvement of other organs as well. 

(h) Cancers of the uterus and some of those of the stomach, 
by reason of the hemorrhage which they produce, are apt to be 
associated with a very high leucocyte count. 

(c) Tumors of the thyroid and of the pancreas are said by 
some writers to cause a specially great leucocytosis. Li my own 
experience, tumors of the kidney have shown very marked in- 
crease of white cells. 

2. Size. — Other things being equal, the larger and more 
rapidly growing tumors show in most cases a greater leucocy- 
tosis than small, slow-growing ones. 

Thus the cancers of the lip and of the pylorus, scirrhus of 
the breast or of the penis, show smaller counts than tumors of 
the liver, omentum, and kidney, which are apt to grow more 
rapidly. Metastases in the bone marrow are thought by some 
observers to give peculiar qualitative blood changes (see be- 
low) . 

In general, metastases, being a method of rapid growth, 
simply add to the leucocyte count. 

These distinctions eliminate some of the apparent contradic- 
tions between the findings of different individuals who were 
simply describing cancers of different types. But even within 
a single type, there are very marked differences in different 
cases. For instance, Alexander' found the leucocyte count in 
cases of scirrhus of the breast to vary between 2,360 and 21,700. 
Similar differences have been reported in cancers of the stomach 
{e.g., Schneider^ finding leucocytosis in aU of twelve cases, while 

1 Alexander : These de Paris, 1887. 
- Inaug. Dissert., Berlin, 1888. 



CANCER OF THE BREAST. 



295 



Osterspey' in another series of twelve cases found leucocytosis 
in only two). 

3. Besisting Power. — Possibly a part of these differences is 
to be explained by differences in the resisting power of the in- 
di'sidua] . But if this is so, we cannot measure the endurance of 
a given patient by his general health. As in the Civil War the 
pale, city -bred men outlasted the healthy farmers, so here the 
tumor's rapidity of growth seems often to be greatest in the 
most vigorous young individuals, while dried-up old women will 
resist its advance for a longer period. 

We come now to the conditions to be found in particular 
types of cancerous growth. 

Surprisingly little w^ork has been done on the blood in malig- 
nant disease, such cases usually being under the charge of sur- 
geons who rarely value such investigations. Except for scattered 
counts here and there, all our knowledge of the corpuscles rests 
on the work of Hayem and Alexander in France, and Eieder, v. 
Limbeck, Pee, Sadler, Eeinbach, Osterspey, Grawitz, Strauer, 
Schneyer, and Schneider in Germany. 

CANCER OF THE BREAST. 

Most of our data come from Hayem^ and his pupil Alexan- 
der. ' 

1. Scirrhus Ghroiuths. — Number of cases, 14. Average leu- 
cocyte count, 11,400. Highest count, 21,700; lowest, 2,360 — the 
last is somew^hat doubtful as to diagnosis; except for this case, 
which was in a very old, dried-up woman, the low^est count was 
7,400. 

In 10 out of the 14 cases, the count was over 10,000. In the 
3 cases seen by the writer 2 showed no leucocytosis, 1 a consid- 
erable leucocytosis. 

2. Medullary {Enceplialoicl) Ghrowtlis. — Three cases, all over 
10,000— average 11,300. 

^ Inaug. Dissert. , Berlin, 1892. 

2 Hayem : "Du Sang," Paris, 1889, p. 947. 

^ G. Alexander: "De la Leucocytosis dans les Cancers," Paris Thesis, 
1887. 



296 



SPECIAL PATHOLOGY OF THE BLOOD. 



Effects of Operation. 

The following figures from Hay em are also of interest : 
Case I.— Scirrhus of the Breast. 

Before operation 21,700 

Five weeks after operation (wound not 

quite healed) 10,000 

Wound completely healed 6,200 

Seven months after operation 8,990 (beginning to rise again) 

The growth recurred some months later and leucocytosis was again 
present. 

Case II. — Scirrhus of the Breast. 

First Second 
count. count. 

Before operation 11,500 11,450 

After operation 8, 500 6, 200 

Case III. — Scirrhus of the Breast. 

First Second 

count, count. 

Before operation 11,000 12,400 

After operation 8, 400 

Case IY. — Scirrhus of the Breast. 

Before operation 7,400 

After operation 1,300 

Case V. —Medullary Cancer of the Breast. 

Before operation 10,000 

After operation 9, 000 

Hay em considers that by watching the leucocyte count wo 
can predict the coming of a recurrence before any physical signs 
are present. This he did in Case I. of the series just given. 

I have seen no confirmation or refutation of this statement. 
It is one of the many points to which the attention of surgeons 
should be directed. 

CANCER OF THE STOMACH. 

Here we have a much larger body of data to judge from. 
Thus: 

Hayem^ in 12 cases found leucocytosis present in 5, absent 
in 7. 

1 " Du Sang, " Paris, 1889, p. 948. 



CANCER OF THE STOMACH. 



297 



Schneider' in 12 cases found leucocytosis in 12 (all). 

Sclmeyer'' in 18 cases found leucocytosis in 4, and these 4 all 
under 11,000. 

Osterspey' in 12 cases found leucocytosis in 5. 

Eieder"^ in 6 cases found leucocytosis in 3. 

Sadler' in 13 cases found leucocytosis in 2, and in both there 
were complications (abscess of liver, perforation of gullet with 
gangrene) to which the leucocytosis might be due. 

Reinbach' in 4 cases found leucocytosis in 2. 

Reinert ' in 2 cases found leucocytosis in 2. 

Laache^ in 5 cases found leucocytosis in none. " 

Despite these facts we have the record of a certain number 
of single cases in which the leucocytosis has been enormous. 
For instance, Welch in "Pepper's System of Medicine" men- 
tioned a case in which the ratio of white to red cells was 1 : 25 
(normally 1 : 750 + ). Eisenlohr's ^ case showed 1 white to 50 red 
and Potain's'" case showed 1 white to 48 red cells. 

The Massachusetts Hospital series of 46 cases showed leuco- 
cytes in 15 cases and none in 31 (see Tables XXXIX., A, B). 
Out of those showing leucocytosis 6 were under 12,500, that is 
the leucocytes were but slightly increased, leaving only 9 out 
of 45 (or twenty per cent) in which the leucocytosis was very 
marked. Among these 9, the highest counts were 40,000 and 
39,000, and the highest ratio 1 : 62. 

In this series I have excluded all cases in which there was 
evidence of metastasis in other organs ; this means excluding 7 
cases, 6 of which showed leucocytosis, and helps to account for 
the low average leucocyte count in the other 46 cases. 

In over three-fourths of these cases the diagnosis was made 
certain either by operation or by autopsy ; all the others showed 

^ Inaug. Dissert., Berlin, 1888. 
2 Inaug. Dissert. , Berlin, 1892. 
2 Loc. cit. 

^ Original-Mittheilungen aus der Klinik v. Jaksch, 1891. 
5 Langenbeck's Archiv, 1893, p. 486. 
^ Loc. cit. 

*'Die Anamie," Christiania, 1883. 
^ Apparently, since he draws attention to the fact that there is leuco- 
cytosis in a case of cancer of the uterus. 

9 Deut. Arch. f. klin. Med., 1877, vol. xx. 

10 Gaz. des Hop. , 1888, No. 57. 

20 



298 



SPECIAL PATHOLOGY OF THE BLOOD. 



either a palpable tumor in old cachectic patients with pain and 
vomiting, or other equally clear evidence for the diagnosis. 
Doubtful cases have been excluded. As will be seen by the 
table, in some of the cases the counts were verified by repeated 
examinations, while in others only a single count — that made 
■when the patient entered the hospital — was recorded. 

As a rule, the high leucocyte counts were in the more cachec- 
tic cases; but this does not always hold. Cases 10, 11, and 
28 in Table XXXIX., A, were very cachectic but showed no 
leucocytosis. 

The position of the tumor in one or another part of the 
stomach seemed to have no connection with the number of leu- 
cocytes. 

On the whole, leucocytosis is relatively infrequent in cancer 
of the stomach, occurring in only about one-third of the early 
cases. As the disease progresses we may get a leucocytosis, par- 
ticularly in case its growth is rapid and metastases are frequent 
and numerous ; but some cases, particularly those in which the 
tumor is small and grows slowly, may run their entire course 
without any leucocytosis being present. In this respect they 
are like the majority of small, slow-growing cancers in other 
parts of the body (see below). 

Hemorrhage or perforation is of course accompanied by an 
increase in the number of white cells — in fact the highest count 
in the present series (105,600) occurred in a case in which a can- 
cer of the stomach with metastases in the liver perforated into 
the peritoneal cavity and started a virulent, quickly fatal peri- 
ionitis. 

DIGESTION LEUCOCYTOSIS IN CANCER OF THE STOMACH. 

A considerable body of statistics has accumulated to show 
that in the great majority of cases of gastric cancer the leucocy- 
tosis of digestion (see above, page 84) does not occur. R. 
Miiller ' noticed this fact in 5 cases of cancer of the stomach. 
8chneyer ' in 18 cases found it invariably absent, while in 3 cases 
of benign stenosis of the pylorus a considerable digestion leuco- 
cytosis appeared, as was also the case in 7 out of 8 cases of 
ulcer of the stomach. 

' Prag. med. Woch., 1890, No. 17. 

'-^ Zeit. f. klin. Med., 1895, p. 475. 



CANCER OF THE STOMACH WITH METASTASES. 299 

He found botli incipient and advanced cases to be similarly 
affected. In 5 of his cases and in some of Miiller's HCl was 
present in the gastric contents, so that the absence of diges- 
tion lencocytosis was not due to absence of HCl. 

Hartung (Wiener Uin. Woch., p. 697, 1895) in a series of 10 
cases (mostly advanced) found no digestion leucocytosis. 

Capps ' in 14 cases examined at the Massachusetts General 
Hospital found a digestion leucocytosis in 2, the increase being 
respectively 4,100 and 3,850 cells over the count before the be- 
ginning of digestion. In the other 12 cases there was no in- 
crease after a large proteid meal. 

Two cases of ulcer of the stomach showed marked increase, 
as did several cases of hyperacidity and other gastric disorders 
(see Diseases of the Stomach, page 241). 

CANCER OF THE STOMACH WITH METASTASES. 

Most writers have not separated the cases with metastasis 
from those without it. A glance at the seven cases of Table 
XXXIX., C, shows that with one exception leucocytosis was 
present throughout most of the disease. 



Table XXXIX., C— Cancer of the Stomach with Metastases. 



d 


Age. 


w 


Red cells. 


White 
cells. 


Per cent' 
haemo- 
globin. 


Remarks. 


1 


48 


M. 


4,238,000 


5,000 
6,200 
7,300 
10,000 
10,190 
13,653 

7,000 
14,400 
19,600 


70 


January 23d. Stomach and liver. 
January 28th, mealtime, 
January 28th, three hours later. 
Stomach, liver, and glands. 
January 6th. Stomach and liver, 
January 12th. 
January 22d, died. 
February 14th, no cachexia. 
March 6th, liver involved. 
March 12th. 












2 
3 


41 

38 


M. 
M. 


4,272,009 
5,432,000 


57 
52 


4 


66 


M 




70 






5,168,030 


62 










21,640 
16,000 
24,000 
24,200 
22,500 
34,350 

30,600 
105,600 ' 




March 17th, cachectic. 
Stomach, liver, and spleen. 
Stomach and liver. 

November 7th, cancer of stomach 

and liver. 
November 11th. 


5 


Adult. 


M. 


3,352,000 
4,160,000 




6 
7 


54 
47 


M. 
M 


60 




















November 14th, perforation peri- 
tonitis. 















^ Boston Med. and Surg. Journal, 1896. 



300 



SPECIAL PATHOLOGY OF THE BLOOD. 



CANCER OF THE GULLET. 

Most authors are agreed that no increase — in fact usually a 
decrease — of white cells is the rule in this disease. Thus Rie- 
der found 6,900 in one case; Osterspey's two cases showed no 
leucocytosis, and Eschericli and Pee found similar results.' 
This is probably due to the fact that the position of the tumor, 
by causing starvation, tends to lower the leucocytes, while it be- 
longs to the class of small, slow-growing cancers which do not 
as a rule tend to produce leucocytosis. 

Nevertheless, two of the five cases in the Massachusetts Hos- 
pital series (see Table XL.) did have leucocytosis, perhaps owing 
to some metastasis or complication. There was no autopsy in 
either. 



Table XL.— Cancer of the Gullet. 



d 


Age. 


[ Sex. 1 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


58 


M. 


5,488,000 


6,800 


100 (!) 


May 18th. 










6,800 


May 11th. 


2 


56 


M. 


4,920,000 


8,725 


72 


3 


51 


M. 


2,824,000 


7.600 


50 


Before food. 








11,500 




Four hours after. 


4 


67 


M. 


4,604,000 


16,400 


60 


One and one-half hours after food. 


5 


38 


F. 


4,560,000 


20,600 


50 





CANCER OF THE LIVER. 

(See Table XLI.) 

Out of fourteen cases, leucocytosis was present in eight — a 
larger proportion than in gastric cancer. The cases were not 
all primary in the liver or bile ducts, but none originated in the 
stomach, and in all the greater part of the growth was in the 
liver itself. 

The comparatively great diminution in the red corpuscles 
will be noted in the Table XLI. The condition both of red and 
white cells is doubtless due to the rapid growth of tumors of the 

^ Reinbach's two cases showed a diminution in the polymorphonuclear 
cells, which in all probability means a normal or diminished leucocyte 
count. 



CANCER OF THE INTESTINE. 301 

liver as compared, e.g.^ with those of the stomach or lip (see 
below). 



Table XLI.— Cancer of the Liver. 





Age. 


X 

CD 
02 


cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


55 


M. 


4,170,000 


5,000 


52 


Bile ducts= starting-point. Autopsy. 


2 


61 


M. 


3,824,000 


5.200 




3 


59 


M. 


4,570,000 


8,000 




Operated. 


4 


72 


M. 


4,100,000 


9.000 






5 


44 


F. 


4,952,000 


7,800 


69 


January 4th, 1896. Autopsy. 








3,784,000 


19,700 
9,300 


68 


February 12th, 1896. 


6 


54 


M. 


4,072,000 




Differential count of 1,000 cells: Poly., 82.4 per 












cent ; small lymphocytes, 8.5 ; large lympho- 














cytes, 8.1; old lymphocytes, 1. 


7 


50 


M. 


3,200,000 


10,800 




Primary in bile ducts. Autopsy. 


8 


? 


M. 


4,108,000 


9,970 


45 


January 1, 1896. 








11,200 




January 3d, 1896. Autopsy. 


9 


43 


M. 


4,160,000 


14,100 


? 


July 17th, 










July 19th. Autopsy 


30 


64 


M. 


2,768,000 


15,800 


45 


May 6th. 








2,880,000 


21,900 




May 24th. 










1,530 


45 


May 28th. 








2,928,000 


11,700 




June 8th. 


11 


35 


M. 


3,800,000 


9,800 




November 3d. 








22,000 




November 5th. 












November 6th. Differential count of 500 cells: 














Poly., 92 per cent; lymphocytes, 8. Autopsy. 


12 


48 


F. 


2,900,000 


17,500 


48 


Differential count of 500 cells: Poly., 92 per cent; 










lymphocytes, 5.8 ; eosinophiles, .2 ; myelo- 














cytes, 2. Autopsy. 


13 


Adult. 


M. 


4,408,000 


25,500 


70 


14 


50 


M. 


4,544,000 


35,600 




November 29th, 1895. 








36,400 




December 10th, 1896. 








3,136,000 


23,000 




January 15th. 1896. 








4,056,000 


28,800 




February 16th, 1896. Autopsy. 



CANCER OF THE INTESTINE. 

Here the counts range both high and low. 

Hay em' found cancer of the rectum to show only 9,500 
leucocytes. Eeinbach ^ found in three cases of cancer of the rec- 
tum moderate leucocytosis.^ Only two of the seven cases in our 
series (see Table XLII. ) showed leucocy tosis and in one of these 
there was a complicating pylephlebitis which probably raised 
the count. 

The red cells show little change. 

* Loc. cit. 

* Loe. cit. 

^ Apparently — that is, the percentage of adult cells was increased. He 
did not count the leucocytes as a whole. 



302 



SPECIAL PATHOLOGY OP THE BLOOD. 
Table XLII.— Cancer of the Intestine. 



Age. 


X 

cc 




M. 


41 


F. 


31 


M. 


33 


M. 


59 


F. 


66 


M. 


50 


F. 



Red 
cells. 

4,408,000 

5,560,000 
4,921,000 
4,368,000 
4,800,000 
4,268,000 
5,416,000 



White 
cells. 

12,700 

5,800 
8,800 
5,800 
5,500 
7,150 
12,000 



Per cent 
haemo- 
globin. 



Remarks. 



Cancer of duodenal papilla with pylephlebitis. 
Autopsy. 

Cancer of caecum. Operated successfully. 
Cancer of hepatic flexure. Operated. 
Cancer of colon. Operated. 
Cancer of caecum. Autopsy. 
Cancer of intestine (where ?). 
Cancer of rectum. 



CANCER OF OMENTUM AND ABDOMINAL ORGANS GENERALLY. 

The seven cases seen at the Massachusetts General Hospital 
in which cancerous tissue was prett3^ generally distributed 
through the abdominal organs, all showed leucocj^tosis with 
one exception, the counts ranging high (see Table XLIII., A 
and B). 



Table XLIII., A. 



-Cancer of Omentum and Abdominal Organs 
Generally. 



Age. 



50 



65 
Adult. 
Adult. 

45 
Adult. 



Red 
cells. 



3,772,000 
5,500,000 



White 
cells. 



Greatly 
ncreased 



9,000 
11,700 
13,700 
26,200 
27,400 
Greatly 
increased 



Per cent 
haemo- 
globin. 



Markedly 
diminished, 



Markedly 
diminished 



Remarks. 



Primary in pancreas. Differential count of 
400 cells: Poly., 84.5 per cent; small lym- 
phocytes, 8; large lymphocytes, 5; eosino- 
philes, 2.5. Autopsy. 



Autopsy. 
Autopsy. 

Question of aneurism. Autopsy. 
Differential count of 500 cells: Poly., 80 per 
cent; lymphocytes, 20. 



CANCER OF THE KIDNEY. 

Of four cases which I have examined (see Table XLIII., B) 
all showed very large leucocyte counts — viz., 27,000, 28,500, 43,- 
100, 82,000, and 91,000, an average of 54,000. In two of these 
cases, however, the tumors may have been sarcomata, as no 
microscopic examination was made. Most of the cases had 



CANCER OF THE UTERUS. 



308 



fever, chills, and signs of inflammation, which may account for 
part of the leucocytosis. 



Table XLIII. , B.— Cancer of Kidney. 



Remarks. 



Differential count of 500 cells: Poly., 66 per 
cent; lymphocytes, 29.5; eosinophiles, .2;: 
myelocytes, 2.5; normoblasts, 24; megalo- 
blasts, 2. Autopsy. 
Supposed leukaemia. Differential count of 50O 
cells: Poly., 81.8 per cent; small lymphocy- 
tes, 13; lai-ge, lymphocytes. 4.2; eosino- 
philes, 2. Autopsy. 
Supposed leukaemia. Differential count of 
1,000 cells: Poly., 92.9 percent; lymphocy- 
tes, 6.2; myelocytes, .9; normoblasts, 2; me- 
galoblasts, 1. Autopsy. 
July 8th. 

Poly. , 98 per cent ; lymphocytes, 2. 

Von Limbeck's ' case mounted steadily from 18,514 to 
80,541. 



CANCER OF THE UTERUS. 

In six cases Hayem ^ found no increase — the counts ranging 
from 4,575 to 9,500 with an average of 7,800. 

Eieder,^ on the other hand, in a single case found 30,800, and 
the three cases counted at the Massachusetts Hospital showed 
respectively 19,400, 22,250, and 34,900 (see Tables XLIV., A 
and B). 

There is need of more data on this subject. 



Age. 


Sex. 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


2 


F. 


3,756,000 


27,000 




57 


F, 


5,200,000 


28,500 




49 


F. 


3,360,000 


43,100 




50 


F. 


4,111.000 


82,000 








2,780,000 


91,000 





Table XLIV., A. — Cancer of the Uterus. 





Age. 


Sex. 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


2 
3 


48 
51 

31 


F. 
F. 

F. 


2,696,030 
3,232,000 


19,400 
30,700 
34,900 

22,250 


20 
27 


October 26th. 
October 28th. 

Differential count of 1,000 cells: Poly., 88 per 
cent; small lymphocytes, 11.7; eosino- 
philes, .2; myelocytes, .1. Two normoblasts. 


2,889,680 





' Loc. cit. 



2 Loc. cit. 



2 Loc. cit. 



304 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XLIV., B.— Cancer of the Ovary. 



d 


Age. 


Sex. 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 


36 


F. 
F. 


4,500,000 
3,248,000 


25,000 
32,800 


62 


Operation. 
Operation. 



45 1 M. I 



t I 51 I M. I 7,000,000 



Cancer of the Prostate. 

I 10,200 I 1 

Cancer of the Lip. 

),300 I I 

Cancer of the Breast. 



1 


31 


F. 


6,000,000 


8,000 




? 


F. 


Not 










increased 




? 


F. 




Marked 










increase. 



42 M 



Differential count of 600 cells: Poly., 72.4 
percent; lymphocytes, 25.4; eosinophiles, 
2.2. 

Differential count of 400 cells: Poly., 89 per 
cent; lymphocytes, 11. 



Cancer of the Neck. 

Marked I Poly., 88.5 per cent. 

increase. 



Cancer of the lip has apparently been neglected so far as 
Wood examination is concerned. Hayem, Eieder, and Reinbach 
give but one case each, the counts being respectively 7,000, 11,- 
600, and "not increased." In a single case at the Massachu- 
setts Hospital I found 6,300. 

The following scattered counts may be added: Cancer of 
tongue, 7,000 (Hayem); cancer of scrotum, 6,700 (Hayem); 
cancer of navel, 7,100 (Hayem); cancer of larynx, 7,200 
(Hayem), 16,000 (Reinbach); cancer of ovary, 25,000 (Massa- 
chusetts Hospital) and "no increase" (Reinbach); cancer of 
neck, 20,000 (Massachusetts Hospital) and "no increase" (Rein- 
bach); cancer of pancreas: Hayem, 2 cases — 9,400 and 9,900; 
Schneider, 1 case — 12,000; cancer of vagina, 9,800 (Rieder) ; 
cancer of penis, 7,000 (Hayem); cancer of thyroid, 70,000 
(Hayem) (a very rapidly growing tumor) ; cancer of media- 
stinum, "marked increase" (Reinbach); cancer of prostate,^ 
10,200. 

^ Braun (Wien. med. Woch., 1896, p. 582) mentions a cancer of the 
prostate in whichthe leucocytosis instead of being made up mostly by the 
adult leucocytes, was associated with a large increase of the small lympho- 
cytes together with numerous eosinophilic myelocytes. 



CANCER OF THE UTERUS. 



305 



Qualitative Changes hi the Leucocytes. 

1. Whenever leucocytosis is present we find, as in most path- 
ological leucocytoses, a marked increase of the adult, at the ex- 
pense of the young, cells. 

Keinbach found in 8 cases with leucocytosis 89 per cent in 
2 cases and 87, 86, 83, 81, 80, and 77 per cent in others. In 
^;hb Massachusetts General Hospital series the following per- 
centages occurred: When no leucocytosis was present 62.5 and 
62 per cent. With leucocytosis, 96, 98, 92, 86, 84 per cent, 
etc. (See Tables XXXIX., XLI., XLIH., XLIV.) 

2. Eosinophiles are not always notably decreased (as they are 
in many other leucocytoses) nor are they increased except when 
bone metastasis occurs (see below). In Eeinbach's 16 cases the 
average percentage was 2 + per cent. In the Massachusetts Hos- 
pital cases the average was 1.2 per cent, but in 4 of the 14 cases 
in which differential counts were made, no eosinophiles were 
seen. 

3. Myelocytes. — Perhaps more commonly than in other con- 
ditions except leukaemia and pernicious ansemia, we find in ma- 
lignant disease small percentages of myelocytes, as the following 
cases show : 

Case I. — Extensive abdominal cancer ; great cachexia. Six 
hundred cells showed: 

" Polynuclear neutrophiles" ^ 89.4 per c©nt. 

Lymphocytes 10. " 

Eosinophiles ,1 " 

Myelocytes (3 in 600 cells) 5 

Case II. — Cancer of uterus; marked cachexia and leucocy- 
tosis. One thousand cells showed : 

"Polynuclear neutrophiles" 82.3 per cent. 

Lymphocytes 17.3 " 

Myelocytes (4 in 1,000 cells) 4 " 

Case III. — Cancer of uterus; died two days later. Red cor- 
puscles, 7,000,000; white, 62,000. Considerable stasis helps to 
explain the count. Differential count of 500 cells showed : 

" Polynuclear neutrophiles" 93 per cent. 

Lymphocytes 6 " 

Eosinophiles 0 " 

Myelocytes (5 out of 500) 1 " 



306 SPECIAL PATHOLOGY OF THE BLOOD. 

Case IV. — Cancer of liver, jaundice and cachexia; died soon 
after. Differential count of 500 cells showed: 

" Polynuclear neutrophiles" 92. per cent. 

Lymphocytes 6. " 

Small myelocytes , 1.2 " 

Large myelocytes (4 in 500) .8 " 

Case Y. — Cancer of abdomen ; cachectic. Differential count 
of 1,000 cells showed: 

" Polynuclear neutrophiles" o 82. per cent. 

Lymphocytes 16.6 " 

Eosinophiles 1, " 

Myelocytes (4 in 1,000) 4. 

Case VI. — Cancer of stomach, liver, etc., with perforated 
stomach; cachexia. Leucocytes, 105,000. Fifteen hundred 
cells showed : 

" Polynuclear neutrophiles" 90.7 percent. 

Lymphocytes , 4.8 " 

Eosinophiles 2 " 

Myelocytes (68 in 1,500) 4.3 

Case VII. — Cancer of uterus; cachexia. In 1,000 cells them 
were : 

"Polynuclear neutrophiles" 88. percent. 

Lymphocytes 11.7 " 

Eosinophiles 2 " 

Myelocytes 1 " 

Case VIII. — Cancer of kidney; great cachexia. In 1,000 
cells there were : 

" Polynuclear neutrophiles" 92.9 per cent. 

Lymphocytes 6.2 " 

Myelocytes 9 " 

Case IX. — Cancer of kidney; great cachexia. Leucocytes. 
27,000. Five hundred cells showed: 

"Polynuclear neutrophiles" 66. percent. 

Lymphocytes 29.5 " 

Eosinophiles 2. " 

Myelocytes 2.5 " 



SARCOMA. 307 

Case X. — Cancer of liver. Five hundred cells showed: 

" Poly nuclear neutrophiles" 92. percent. 

Lymphocytes 5. 8 " 

Eosinophiles 2 " 

Myelocytes 2. " 



Whether there is any reason to suspect bone metastasis in 
these cases I do not know. There were no examinations of the 
bones made post mortem. 

Epstein (Wiener med. Presse, December, 1894) in a case of 
cancer with metastatic bone nodules noticed large numbers of 
nucleated corpuscles (normoblasts and megaloblasts) and mye- 
locytes. 

SARCOMA. 

In general the effects of sarcoma are like those of cancer, but 
worse. Great anaemia and higher leucocyte counts are the rule. 
The literature of the subject is rather scanty. 

Red Cells. — Hay em in a case of osteosarcoma counted the 
red cells at 663,400 per cubic millimetre. 

Laker' describes an " abdominal cystosarcoma" in which two 
counts of red cells showed 2,800,000 and 2,500,000. 

Yon Limbeck"^ in 1 case found 1,118,000, and in another 2,- 
240,000. Both were osteosarcomata. 

Sadler^ in 3 cases found 2,710,000, 3,637,000, 4,500,000. 

Eieder'' in 3 cases (all osteosarcomata) found 1,846,160, 3,- 
770,000, and 3,995,000. 

The Massachusetts Hospital blood counts include 12 cases 
in which the red cells were counted (see Table XLY. , A and B) , 
the average being 4,400,000, not nearly so low as that recorded 
by other observers; still low counts occurred (2,706,000, 2,637,- 
000, 3,842,000). 

The qualitative changes in the red cells consist (as in cancer) 
of the "degenerative" changes (deformities in size and shape, 
englobular changes) present in marked cases, and the presence 
of nucleated corpuscles, when cachexia is marked. 

1 Wien. med. Woch., 1886, p. 926. 

2 Loc. Git, p. 343. 

3 Loc. cit. , pp. 38, 39. 
^Loc. cit, pp. 98, 100. 



308 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XLV., A.— Sarcoma with Leucocytosis. 



Age. 



Red 
cells. 



White 
cells. 



Per 
cent 
haemo- 
globin. 



Remarks. 



48 



57 
Adult. 



2,706,000 
4,560,000 



4,700,000 

2,630,000 
2,900,000 
4,352,000 
3,842,000 
6,200,000 



4,180,000 



56,000 
17,000 



23,900 
33,400 
37,900 
41,200 
33,000 
36,000 
40,200 
55,400 
16,000 
19,000 
24,000 
21.000 
13,600 
61,100 
16,000 
Marked 

in- 
crease. 
13,000 
16,250 
15,180 
18,000 
Great 

in- 
crease. 
Great 

in- 
crease. 
13.200 



47 



Sarcoma of kidney. Autopsy. 

3Ielanotic sarcoma all abdominal organs (bone 
metastasis ?). November 30th, 1895. Differen- 
tial count of 600 cells: Poly., 71 per cent; 
small lymphocytes, 11; large lymphocytes, 5.2; 
eosinophiles, 12.4 (! ) ; myelocytes, .4. 

December 7th. 

December 13th. 

December 19th. 

December 22d. 
December 26th. 
January 14th. 
January 28th. 

Sarcoma of abdominal organs. 

Three days later. Autopsy, 

General sarcomatosis. 

One week later. Autopsy. 

Sarcoma of kidney. 

Sarcoma of lung, etc. Autopsy. 

Sarcomatosis. 

Differential count of 700 cells : Poly. , 70 per cent; 

lymphocytes, 22; eosinophiles, 1 ; myelocytes, 7. 

Sarcomatosis. 
Melanotic sarcoma of abdominal organs. 
One week later. 

Sarcoma of abdominal organs. 

Osteosarcoma (thigh). Differential count of 500 
cells: Poly., 74 per cent; small lymphocytes, 19; 
large lymphocytes, 6; eosinophiles, 1. 

Sarcoma of abdominal organs. Differential 
count of 800 cells : Poly. , 84 per cent. ; lympho- 
cytes, 15.5; eosinophiles, .5. 

Sarcoma of abdominal wall. 



Table XLV., B.— Sarcoma without Leucocytosis. 



d 


Age. 


Sex. 


Red 
cells. 


White 
cells. 


Per 
cent 
haemo- 
globin. 


Remarks. 


1 


29 


M. 


5,280,000 


8,200 




Sarcoma of testicle. 


2 


37 


F. 


4,980,000 


9,000 


78 


Sarcoma of ovary. 


3 


? 


M. 


4,946,000 


9,000 




Osteosarcoma of shoulder. 


4 


24 


M. 


4,952,000 


6,000 




Small recurrent sarcoma of groin. 



Small tumors are often without any effect on the blood (see 
Table XLY. , B) . According to v. Limbeck' this is oftener true 
than in cancer. 

Hcemoglobin. — Eeinbach's'^ 20 cases ranged between 23 and 75 
per cent, averaging 52 per cent. 



' Log. cit. 



2 Log. Git. 



SARCOMA. 



309 



Bierfreund ' in 29 cases found variations between 40 and 75 
per cent. 

Von Limbeck's 2 cases had 28 and 48 per cent respect- 
ively. 

Eieder's^ 4 cases showed at the beginning of treatment 29, 
56, 57, and 65 per cent respectively, but in 1 case the haemoglobin 
went down gradually while under observation until it reached 
6 per cent (!), the lowest point, Kieder says, that he has ever 
seen in any disease. 

Sadler' s^ cases showed 33, 45, and 78 per cent. 

In the 5 cases of Table XLY. in which this point was noted, 
the average is 58 per cent. 

On the whole, the coloring matter seems to be more dimin- 
ished than in most cases of cancer. 

Leucocytes. — The following tables, slightly modified from 
V. Limbeck, show the important points. 

For other sarcomata, see Tables XLY., A and B. 

On the whole, leucocytosis appears to be more constant and 
of greater extent in sarcoma than in cancer. 



No. 


Observer. 


Diagnosis. 


Count. 


1 


Hay em. 


Osteosarcoma. 


11,250 


2 


Alexander. 




52, 700 


3 






16,430 


4 


u 




16,275 




(( 




17, 050 


5 






15,900 








15,570 


6 






18,020 


7 






10,950 








12, 090 


8 






11,248 


9 


Rieder. 




12,700 




u 




10, 900 


10 






9.100 


11 


u 




8,000 


12 


V. Limbeck. 




32, 000 








26,800 


13 


Reinbach. 




20, 000 


14 


u 




13,000 


15 


Massachusetts Hospital. 




21,000 


16 






9,000 






Average, 


17,000 ± 


^ Loc. cit. 2 x^QQ^ czY. 


2 Loc. cit. 



310 



SPECIAL PATHOLOGY OF THE BLOOD. 



No. 


Observer. 


Diagnosis. 


Count. 


1 




Hay em. 


Lympiiosarcoma. 


1 1 TAA 


2 




.A-lexan der. 


19,910 


3 




tk 


" 


19! 530 


4 








11,696 






u 




11,470 


6 








10, 540 


7 




V, Limbeck. 




55,100 


8 








38, 000 


9 








10,800 


10 




Sadler. 




33, 248 


11 






(( 


19,299 


1?. 








9,044 






Average, 


20, 000 -f- 



No. 


Observer. 


Diagnosis. 


Count. 


1 




Rieder. 


Melanosarcoma. 


41,600 


2 








28, 500 


3 








22, 300 


4 




Reinhach. 




25, 000 


5 








8,000 


6 




Massachusetts Hospital. 


it 


37,900 


7 






13, 000 






Average, 


25,100 4- 



Qualitative Changes. 

1. The increase of adult leucocytes which we find in most 
forms of leucoc^^tosis is not always present in sarcoma' and 
seems to be less frequent than in cancer (see Cases II., VIII., 
and XI., Table XLY.). 

As in cancer, it may be present when no increase in the total 
leucocyte is to be found, and may be the only indication of any 
disease in the organism. 

2. A few cases are on record in which a large percentage of 
eosinopliiles has been present. 

Reinbach found 48 per cent of eosinophiles in a case of sar- 
coma of the neck with sloughing and ulcerative endocarditis, the 

1 Palma (Deut. Med. Woch., 1892) reports lymphocytosis in sar- 
coma. 



SARCOMA. 



311 



percentage continuing over 40 for several weeks/ Autopsy 
showed sarcomatous nodules in the bone marrow. In another 
casej a tumor of the abdomen, the eosinophils were 10.5 per cent, 
and in two others 8 per cent. 

A case of apparent sarcoma of the abdominal organs (no 
autoijsy) at the Massachusetts General Hospital in January, 
1896, had 12.4 per cent of eosinophiles. 

Such cases should certainly make us think of bone metas- 
tases, and Neusser speaks of osteosarcomata as being accom- 
panied by eosinophilia, but the evidence is as yet fragment- 
ary. 

3. Myelocytes. — Reinbach's case just described had a low per- 
centage of myelocytes. 

The following cases illustrate the same point : 
Case I. is a case of sarcomatosis in a man in whom sarcoma- 
tous nodules were distributed all over the internal organs and in 
the skin. A differential count of 700 white cells showed in his 
case : 



Typical myelocytes (over l^fi) 2 per cent. 

Small myelocytes (under 15//) 5 " 

Lymphocytes 22 " 

"Polynuclear neutrophiles" 70 " 

Eosinophiles 1 " 



The autopsy showed no special lesions in the spleen, glands, 
or bone marrow, except those due to the sarcomatous nodules. 



^ The full counts are as follows : 



April 4th, 1892. 


May 20th, 1892. 


Red cells 5,396,000 

White cells 120,000 (!) 

Haemoglobin 60 per cent. 


Red cells 4,512,000 

White cells 52, 000 



DIFFERENTIAL COUNTS. 





April 4th. 


May 1st. 


May 20th. 


May 26th. 




Per cent. 


Per cent. 


Per cent. 


Per cent. 




48 


51 


55 + 


51 + 




48 


46 


42 


44 + 


Lymphocytes 


2.7 


2.32 


1.5 


3.2 




1 


.68 


.64 


.8 



312 



SPECIAL PATHOLOGY OF THE BLOOD. 



Case II. — Sarcoma of abdominal wall. Differential count of 
800 cells showed : 

" Polynuclear neutrophiles" 84. per cent. 

Lymphocytes 10.5 " 

Large lymphocytes 5. " 

Eosinophiles 2 " 

Myelocytes 3 " 

CASsni. (No. % Table XLV., A).— Six hundred ceUs con- 
tained : 

" Polynuclearneutrophiles" 71. percent. 

Lymphocytes 16.2 " 

Eosinophiles 12.4 " 

Myelocytes 4 " 



Summary of Blood Changes in Malignant Disease. 

1. Small, slow-growing tumors and the early stages of all 
tumors may have no effect on the blood appreciable by our 
present methods of examination. 

2. In advanced cases the red corpuscles often become thin, 
light, and pale, and finally their number may be greatly de- 
creased, the counts running sometimes as low as in pernicious 
anaemia. In this respect, as in others, sarcomata seem to in- 
jure the blood more than cancers. 

3. The color index is always below 1, but is rarely as low as 
we find it in severe chlorosis. 

4. Normoblasts and megaloblasts (the latter being in the 
minority) may occur, the former even in the absence of severe 
anaemia. Deformities in size and shape are common. 

5. Leucocytosis is present in the cachectic end-stages of 
many cases, but is frequently absent in small tumors of slow 
growth and without metastases. The adult cells are often rel- 
atively increased. 

6. Fibrin is not increased. 



Diagnostic Value, 

1. When we are dealing with an obscure, deep-seated dis- 
ease, if hemorrhage is excluded, the presence of persistent leuco- 
cytosis suggests suppuration or malignant disease (rather than 
tuberculosis or syphilis, for example), and excludes any simply 



MALIGNANT DISEASE. 



313 



functional or hysterical affection. Tlie absence of lencocytosis, 
however, does not exclude malignant disease, though it makes 
suppuration ygij unlikely. 

2. Between malignant disease and suppuration — if the other 
signs and symptoms do not decide — there may be nothing in the 
blood to decide. In decided pyaemia we may get pyogenic cocci 
from the blood by culture, but a negative result would not ex- 
clude the suppurating focus. 

The absence of any increase of fibrin in the blood speaks 
against suppuration, and therefore in favor of malignant disease ; 
but the presence of increased fibrin network is not decisive either 
way, as it may be met with in connection with neoplasms, 
though more common in suppuration. 

3. Between malignant disease and hemorrhage — a marked 
anaemia favors the latter, provided the case is a recent one ; for 
the anaemia of malignant disease is comparatively slow to develop. 
The leucocytes give no help. 

4. Between cancer and ulcer of the stomach, if there has been 
no recent hemorrhage, leucocytosis favors cancer; but its absence 
is of no weight either way. 

The haemoglobin is said to decrease steadily in cancer, v\'hile 
in ulcer it tends to return toward normal after the cessation of 
hemorrhage. 

The presence and persistence of digestion leucocytosis 
speak against cancer, and its absence in favor of cancer. It 
must be remembered, however, that any variety of catarrli or 
dilatation (should such be present) can also prevent digestion 
leucocytosis, and that the latter is not invariably present even in 
health. 

5. Between cancer of the liver or bile ducts on the one hand 
and simple gall-stone colic or gall-stone obstruction, the presence 
of leucocytosis favors cancer. As" usual, however, its absence 
does not exclude cancer, and we must bear in mind that gall 
stones ivitli cJiolangitis may raise the leucocyte count as much as 
cancer. Simple cysts or echinococcus cysts cause no leucocy- 
tosis, nor does syphilis of the liver. 

6. The appearance in the blood of large numbers of eosino- 
philes, myelocytes, and nucleated corpuscles during the course 
of a malignant disease points to a bone metastasis. 

7. When a leucocytosis which has disappeared after removal 

21 



314 



SPECIAL PATHOLOGY OF THE BLOOD. 



of a neoplasm reappears, we may expect recurrence of tlie growth 
shortly. 

8. A steadily increasing leucocytosis in a case of malignant 
disease points to a rapidly growing tumor or to the occurrence 
of metastasis. 

9. Between malignant disease and pernicious anaemia the 
diagnosis rests on the following points : 

I. Color index low in malignant, apt to be high in per- 
nicious anaemia. 

IIo Leucocj^tes often increased in malignant, diminished in 
pernicious anaemia. 

III. Lymphocytes often decreased in malignant, increased in 
pernicious anaemia. 

IV. Average size of red cells often decreased in malignant, 
and often increased in pernicious anaemia. 

Y. If nucleated red corpuscles are present the normoblasts 
are in a majority in malignant disease, and in a minority in per- 
nicious anaemia. 

10. The presence of leucocytosis is against the benignness of 
any tumor. 

11. When no actual increase of leucocytes is present, an in- 
creased percentage of the adult variety among those present may 
have the same significance as a leucocytosis. 



CHAPTEE XI. 



BLOOD PARASITES AND INTESTINAL PARASITES. 

Examination foe the Plasmodium Malaria and its Pkoducts. 

I. Time for Examiimtion. — It is often stated that the organism 
is most easily found during the chill. But this is not the writer's 
experience. During a chill it is often difficult and sometimes 
impossible to find the organisms. Eight hours before or after 
a chill is a much more favorable time, although parasites have 
been found as late as forty-eight hours after the last chill. 
During the chill many organisms retire to the internal organs. 

The number of organisms varies a great deal. In some cases 
they are present in every field of a one-twelfth immersion lens, 
while in others we may find only one after an hour or more of 
patient search. In the majority of the cases occurring near 
Boston, it needs but a few minutes' search to find them if the 
blood be taken within twelve hours before or after a chill, and 
provided no quinine has been lately given. Occasionally in 
mild cases the organisms are very scanty ; and it may be almost 
impossible to find any. The quartan and sestivo-autumnal forms 
of malaria are so rare in New England that I shall not attempt 
to describe the parasites found in them, but shall confine my- 
self mostly to the parasites of common tertian and double ter- 
tian fevers with which I am personally familiar. 

II. Method of Examination. — A slide of fresh blood is pre- 
pared as above described (pages 3-7) and examined with a one- 
twelfth immersion lens.' Lower powers should not be used, 
although in skilful hands they are often sufficient. Portions of 
the slide in which the corpuscles do not overlie each other should 
be chosen for examination. As we pass the slide along beneath 
the lens it is well to be on the lookout for any specially large 
or specially pale corpuscle. Such a one will catch the eye if wo 

^ In cold weather both slide and cover should be warmed before using. 



316 



SPECIAL PATHOLOGY OF THE BLOOD. 



are on the watch for it, even though the slide is being passed 
along verv rapidly, and all such should be carefully examined. 

Another thing to watch for is anything black or dark brown. 
If the slide is not perfectly clean, or if the cover-glass has 
touched the skin in collecting the blood, there will often be black 
spots which make us pull up short and examine, only to find 
that they are bits of dirt. This loses time, and hence, as above 
noted, the importance of care and cleanliness in the earlier stages 
of the process. 

Besides any strikingly i)ale or swollen corpuscle or any black 
dots, we should be on the lookout for any movements in the 
field. Here again cleanliness saves time. In dirty slides I 
have repeatedly found rapidly moving organisms unknown to 
me but clearly not the malarial organism, and w^asted time in 
making sure that they were of extraneous origin. 

III. The Malarial Organism. — {a) " Hyaline Forms." In the 
earlier stages of its growth, i.e., during and soon after the chill, 
the organism is not pigmented, but appears only as a light spot 
in the pale greenish-yellow of the corpuscle. It practically 
is never to be seen outside the corpuscle. All malarial or- 
ganisms are to be found within the corpuscle, and only there. ' 

For those who have not examined many specimens of malarial 
blood it is a very difficult thing to find the organism at this stage 
of its groTsiih, and the number of mistakes in diagnosis is very 
large. 

In the later stages, when the organism has become well pig- 
mented, there is nothing that at all resembles it, and those who 
have seen and watched it a few times can hardly mistake any- 
thing else for it. Not so with the so-called "hyaline" or young- 
est form of the organism. Personally I think the name " hyaline 
bodies" is responsible for a part of the mistakes. We are led to 
expect something more shiny and refractile than the organism 
really is, and so are misled by the brilliant white circles to be 
found at the centre of many normal corpuscles under certain 
conditions of light and partial drying up. Time and again I 
have been asked to look at malarial organisms (always the 
"hyaline" forms), and found nothing more than one of these 
effects of light which can be found in any normal blood, if the 

1 Except degenerate forms and spores at the moment of segmentation 
{rarely to be seen) . Crescents and ovoid bodies are intercellular. 



BLOOD PARASITES AND INTESTINAL PARASITES. 317 



conditions are right. There are certain marks by which we can 
exclude these artifacts from consideration : 

I. They are generally far too numerous to be malarial or- 
ganisms. One usually finds a dozen or more in a field which 
would be almost unheard of with the Plasmodium malariae. 

II. They are generally in the centre of the corpuscle, while 
the young malarial organism is almost never at the centre. 

III. They are almost invariably round, the malarial organism 
being generally more irregular and branching. 

IV. They seem to increase and diminish in size as we focus 
up and down upon them, while the malarial organism only grows 
dimmer or clearer. 

Y. They are, as before mentioned, more brilliantly white and 
shiny than the malarial organism, which has often a faint tinge 
of yellow, although much paler than the surrounding corpuscle 
substance. 

YI. Their edges are sharper, the malarial organism often 
fading off very gradually into the corpuscle color. 

YII. Their movement is different. The malarial organism 
is not at all the only thing to be seen moving in the blood, as 
has sometimes been stated. The red corpuscles have the Brown- 
ian motion, and as they begin to crenate often move very actively. 
But their motion is very different from that of the hyaline 
malarial organism, for the latter changes both its shape and its 
position in the corpuscle quite rapidly, while the motion of the 
light space in an ordinary red cell is a wavy undulation of the 
outlines back and forth without any considerable change of 
shape. 

(b) As soon as the organism gets any pigment (and there are 
very few times in the cycle of a malarial case when there are not 
some pigmented organisms present), the active rapid motion of 
the black pigment dots is unlike anything else seen in the blood, 
and when once recognized can never be forgotten or mistaken. 
It is only when the pigment has ceased moving (owing to the 
death of the organism) that the differentiation between dirt and 
malarial pigment becomes difficult. 

Sometimes it is really difficult to distinguish motionless pig- 
ment in a malarial organism from dirt even on careful scrutiny. 
The best way is to get a fresh slide when the pigment is in 
motion. 



318 



SPECIAL PATHOLOGY OF THE BLOOD. 



To any one fairly familiar with the appearance of pigmented 
forms of malarial organisms, failure to find them in a case of 
malaria is due generally (1) to too thickly spread a layer of 
blood, the corpuscles overlying each other; (2) to not looking 
long enough (Figs. 19 and 20) . 

I have not attempted to go into the marks by which we can 




1 s 3 4 




9 



Fig. 19.— The Parasite of Tertian Fever. 1, Normal red cell ; 2, hyaline form of malarial 
parasite ; 3, 4, 5, pigmented forms of malarial parasite ; 6, 7, segmenting forms of ma- 
larial parasite ; 8, 9, degenerating forms of malarial parasite ; 10, flagellate form of 
malarial parasite. (After Thayer.) 

differentiate the tertian, quartan, and sestivo-autumnal forms of 
the organism — for clinical evidence usually suffices to determine 
this point. For information on this and all the finer points in 
regard to the life history and habits of the organism W. S. 




12 3 4 

Fig. 20.— The Parasite of Quartan Fever. 1, 2, Pigmented forms; 3, segmenting form ; 
4, flagellate form. (After Thayer.) 

Thayer's admirable monograph should be consulted. Here it 
is sufficient to sav that as the paroxysm draws near, the pig- 



BLOOD PARASITES AND INTESTINAL PARASITES. 319 

ment granules begin to work in towards the centre in radiating 
lines until tliey are all collected in a solid black mass. While 
this is going on, the pigment granules not infrequently gather 
into short rod-like masses not at all unlike bacilli. 

Eound the central mass of pigment, indistinct radiating 
divisions may sometimes be seen just before the organism breaks 
up. These divisions have been compared to the petals of a 
flower, but it is very -difficult to see more than the faintest indi- 
cations of such an arrangement in most specimens. The cor- 
puscle itself is by this time wholly lost to sight. 

(c) The next stage, that of segmentation, is less commonly 
seen than those just mentioned, and is only to be satisfactorily 
observed by using a warm stage (vide supra, page 8) and spend- 
ing considerable time on the watch for it. Around the central 
pigment mass we may sometimes see in ordinary specimens 
(without warm stage) the faint outlines of a group of small 
spherical, colorless bodies {vide Fig. 2, 9, Plate I.) which are 
the new generation of young organisms. 

Now we should expect that with the next step in the process 
we should find these young plasmodia free in the plasma or en- 
tering a fresh set of red corpuscles. But in the peripheral cir- 
culation this is rarely if ever observed. Thayer in his immense 
experience has never seen them. The next evidence we have of 
the organism is as a " hyaline" body inside the corpuscle again. 

Almost all stages of the growth of the plasmodium which 
we can watch in the blood drawn from the peripheral circulation 
take place within the corpuscle. It is true that as the pigmented 
organism gets towards its full growth, and before the granules 
have begun to gather at the centre, we may find it very difficult 
to find any trace of corpuscle substance around the margin of 
the Plasmodium. Sometimes we see a ring of non-pigmented 
glistening white substance outside the moving black dots (see 
Fig. 2, 7, Plate I.) standing out light against the darker plasma. 
Whether this be corpuscle substance or not I do not know. It 
is not described or pictured in the standard works on the sub- 
ject. 

Occasionally we do find pigmented bodies wholly outside 
the corpuscle, either partly or fully grown. In the intracorpus- 
cular forms the distinction between plasmodium and corpuscle 
substance is not, I think, so sharp and clear as one would be led 
to expect from the plates in standard works. With average eyes 



320 



SPECIAL PATHOLOGY OF THE BLOOD. 



and lenses the outline of tlie organism, as distinguished both 
from its pigment granules and the surrounding corpuscles, is 
not easy to see. It is the moving pigment granules that attract 
our notice. 

(d) It remains to speak of three comparatively small points : 

1. The presence of flagella. 

2. Pigmented leucocytes. 

3. Crescents. 

1. Toward the end of the life history of a malarial parasite, 
it sometimes makes its presence very obvious in the microscopic 
field by knocking about the surrounding corpuscles with its arms 
or "Jlagella.'" Exactly why and under what conditions it shows 
or fails to show these appendages is not known. They are 
about two or three times as long as a red corpuscle and one- 
third or one-fourth as wide. They are usually to be inferred 
rather than directly seen, as they are nearly transparent. Our 
attention is attracted by an active motion among a group of red 
cells apparently of spontaneous origin. Gradually we make out 
a filmy whip-like tail attached to an adjacent malarial parasite. 
Sometimes there is pigment dotted along the flagellum itseK, and 
then we can make it out much more easily. Its distal end is 
especially apt to be pigmented, and by the help of this pigment 
we make out that it is bulbous, while similar swellings can some- 
times be seen at other points along the flagellum. Such a flagel- 
1am may break off and dart about free among the corpuscles. As 
the pigmented end is sometimes all that we can see of it, this 
gives rise to the appearance of a very small, actively locomotive 
pigmented body free among the corpuscles and its course may 
be followed through several fields. 

When the flagella have ceased moving, their presence is gen- 
erally detected, if at all, by an irregular line of pigment dots 
about 20 fj. long, which will be shown by careful focussing to be 
contained within a nearly transparent membrane. 

Yery often we find a leucocyte in process of closing round 
the flagellated parasite. 

2. Pigmented leucocytes, containing the whole or part of 
malarial organisms or simply blocks or granules of black pig- 
ment, are usually to be found in the blood near the time of the 
chill. The pigment is to be carefully distinguished from the 
granules present in most leucocytes, which in certain lights look 



BLOOD PARASITES AND INTESTINAL PAKASITES. 321 



'quite dark even if unstained, dark enougli to be mistaken for pig- 
ment by the untrained eye. Careful focussing and changing tlie 
light will easily determine which we are dealing with, provided 
we are familiar with the appearances of leucocytes in the fresh 
unstained blood. In certain forms of the disease in which the or- 
ganisms themselves retire to the internal organs, the presence of 





Fig. 21.— The Parasite of ^stivo-Autumnal Fever, 1, Hyaline form ; 2, ring-like form in 
shrunken cell ; 3 shows I'etraction of haemoglobin about the parasite ; 4, 5, develop- 
ment of parasite 6, ~, segmenting parasites; 8, 9, crescents; 10, ovoid body; 11, 
flagellate form. (After Thayer. ) 



pigmented leucocytes may be the only evidence of the disease to 
be found in the peripheral blood and is therefore of the greatest 
importance. 

3. Crescentic forms are not often seen in New England. 
They are found only in the aestivo-autumnal forms of malaria 
which occur chiefly in the South and West and have been seldom 
reported in any Northeastern State except in patients who have 
brought them from the South and West. I have never seen these 
crescentic forms except in the stained specimens of other obser- 
vers, and my ideas of them are mostly second-hand (Fig. 21). 
Full account of them will be found in the monograph of 
Thayer's above referred to. 

Hitherto I have spoken wholly of the appearance of the par- 



322 



SPECIAL PATHOLOGY OF THE BLOOD. 



asites in the fresh unstained blood, this being by far the simplest, 
easiest, and surest way of finding them and the only way of 
studying their development. In cases in which we cannot make a 
microscopic examination at the bedside, we can sometimes pre- 
serve the organism alive between slide and cover-glass, until 
we can get it to the nearest microscope, even if this takes sev- 
eral hours. I have carried specimens in my handbag a whole 
morning and yet found the pigment of the malarial parasite in 
motion at the end of that time. Warm weather favors this. 
When it is necessary to keep the specimen some time before 
examination, it is best to paint on the slide a ring of vaseline or 
any gummy substance, and allow the drop of blood to spread out 
inside this ring so that the margins of cover glass are glued to 
the slide by the oily substance and the entrance of air is pre- 
vented. The cedar oil ordinarily used for immersion lenses 
answers the purpose very well. Both slide and cover should be 
gently warmed before spreading the drop of blood. 

Many physicians who cannot possibly carry a microscope 
about with them can easily find room for a few slides and cover- 
glasses and they may be of great service. 

When specimens have to be sent by mail, or for long dis« 
tances, or in cold weather we have to fall back on dried speci- 
mens prepared as described on page 32, provided always that a 
bedside examination is impossible. These can be stained by 
one of the following methods : 

Leave the specimen for half an hour or more in equal parts 
of ether and absolute alcohol, dry them in the air, stain for 
from one-half to five minutes in a one-half-per-cent solution of 
eosin in sixty-per-cent alcohol, wash in water, dry and stain 
one -half to one minute in concentrated watery solution of 
methylene blue ; wash again in water, dry in filter paper, and 
mount in Canada balsam. 

Personally I have found this method rather unsatisfactory on 
account of the different intensity of different eosin stains and 
the consequent need of finding out by experiment how long 
(within the limits of one-half to five minutes) the specimen is to 
be stained before a distinct yet not violent red color is at- 
tained in the protoplasm of the corpuscles. The blue stains 
the Plasmodium itself in contrast with the pink corpuscle 
substance around it; the pigment granules remain, as in 



BLOOD PARASITES AND INTESTINAL PARASITES. 323 



the fresh specimen, black or brownish black. (See Fig. 3, 
Plate I.) 

In my hands the stain of Plehn has proved much simpler 
and more satisfactory as well as quicker. By this method we 
leave the specimens only three or four minutes in absolute 
alcohol and then stain five or six minutes in the following 
mixture : 

Concentrated watery solution methylene blue 60 

One-half -per- cent solution of eosin in seventy-five-per- 
cent alcohol 20 

Distilled water • 40 

Twenty per cent NaOH 12 gtt. 

Wash in water and mount in Canada balsam. 

The trouble of double staining and the uncertainty as to the 
length of time are avoided by this solution, and the parasites are 
beautifully stained. The ordinary 
Ehrlich-Biondi mixture may also 
be used to demonstrate pigmented 
forms. The organism itself does 
not stain at all with this mixture 
but stands out light against the 
yellow of the corpuscle, the pig- 
ment looking as it does in the live 
parasite. The hyaline forms need 
some other stain for satisfactory re- 
cognition, but it is sometimes con- 
venient to use the same stain for 
the differential count and the ma- 
larial organism, as for instance 
when we have only one cover-glass 
preparation in a case of doubtful 
diagnosis. Fixing the specimen in 
alcohol and ether is here far better than heat; otherwise the 
technique is as above described under Triple Staining (page 33). 
The general appearance of the organism so stained is shown 
in Fig. 22. 

If the organisms are fairly numerous and the technique is 
good we can find them by this method even in preparations 
months old. In general, however, it is very inferior to the ex- 




Fig. 22. 



324 



SPECIAL PATHOLOGY OF THE BLOOD. 



amination of the live organism in the fresh blood, and gives 
many more chances for error. 
So much for technique. 

We often hear reports of fruitless searcli for the parasite in 
the blood of malarial patients, but the regularity with which 
they are found at all the larger hospitals and by all practised 
observers in this and other countries leaves no doubt that they 
are to be found in every case during some portion of the cycle. 
The practice of taking blood during a chill contributes, I believe, 
to the number of unsuccessful endeavors to find the organism ; 
as mentioned above, this is the worst, not the best time to look 
for them. Too thick a layer of blood between slide and cover 
accounts for some failures, as I have found in personal experi- 
ence. 

No doubt, in many cases in which we fail to find the organ- 
ism in supposed malaria a faulty diagnosis is the reason. Many 
of the cases in which latent malaria is supposed to have " come 
out" after a surgical operation are exploded by the negative 
examination for parasites and the positive indications of pus- 
pocketing which are afforded by a marked leucocytosis (never 
present in simple malaria), and the fact of insufficient wound 
drainage is often disclosed in this way. Whenever we see the 
leucocytes increased w^e begin to doubt the existence of an un- 
complicated malaria ; if, furthermore, we see no signs of any pal- 
lor of the corpuscles we doubt the presence of malaria still more, 
as there is no more rapid deglobularizer than the malarial or- 
ganism. 

How long after a chill the organisms may still be found in the 
peripheral blood is difficult to decide, but certainly they can be 
found any time within twenty-four hours after the last chill, 
unless quinine has been given, and sometimes even if it has been 
given. 

Othee Changes in the Blood. 

Red Corpuscles. — The following is from Thayer's remarkable 
monograph : 

" A reduction in red corpuscles follows each paroxysm ; these 
reductions are more marked after the early paroxysms than after 
those occurring later. When a certain degree of anaemia has 



BLOOD PARASITES AND INTESTINAL PARASITES. 325 

been reached the losses per paroxysm are much less. When 
the number of corpuscles is reduced to 2,000,000 or 1,000,000 
there is little tendency toward a further fall ; sometimes there 
may be slight rises in the curve between the paroxysms ; often, 
however, the number of cori)uscles remains stationary for 
weeks. 

" In pernicious cases the number of corpuscles may fall be- 
tween paroxysms." Kelsch has seen the count decrease to as 
small a number as 500,000 per cubic millimetre. The diminu- 
tion is greater the longer the disease lasts and the more in 
tense its manifestations. 

During the paroxysms, particularly the earlier ones, the red 
cells tend to increase in number. 

In tertian and quartan fevers there is a rapid and almost 
complete restitution of the corpuscles during the afebrile 
period. 

In sestivo-autumnal fevers the number of red cells bears a 
direct relation to the number of organisms. Crescentic bodies 
seem to have no influence on the number of red cells. 

When after a paroxysm the number of corpuscles has been 
greatly diminished the succeeding paroxysm may be followed by 
a slight reduction only or even by an increase. 

Bignami and Dionisi distinguish three types of post-malarial 
anaemia : 

1. Ordinary secondary anaemia, but with leucopenia instead 
of leucocy tosis ; such cases usually recover. 

2. Anaemia practically identical with pernicious anaemia, 
megaloblasts being present, and ending fatally. 

3. Anaemias which are progressive, because the bone marrow 
cannot compensate for the losses of corpuscles. 

The rapidity of the diminution in red cells may be very great. 
Kelsch' s count of 500,000 cells per cubic millimetre, mentioned 
above, was after thirty days' illness. Grawitz has seen a loss of 
4,000,000 cells in six days. 

Qualitative changes are those of severe secondary anaemia, 
deformities in size and shape, normoblasts, occasional megalo- 
blasts in the worst cases, motility in the " pale, ghostly" cells. 

Hcemoglohin. — The loss of haemoglobin bears usually a direct 
relation to the number of parasites in the blood. As a rule, the 
corpuscles and haemoglobin are diminished proportionally (color 



326 



SPECIAL PATHOLOGY OF THE BLOOD. 



index =1) but sometimes the liEemoglobin is reduced disi^ro- 
portionately. 

In convalescence tlie restitution of hsemoglobin is often in- 
complete; persons liTing in malarial districts have often a 
slightly smaller percentage of haemoglobin than those living 
elsewhere. 

The rapid diminution in haemoglobin is a valuable point in 
differential diagnosis between malaria and typhoid or jmeu- 
monia. 

White Cells. — The number of leucocytes is usually subnor- 
mal, but show a slight increase at the beginning of the x^ar- 
oxysm. Following this increase there is a rapid decrease con- 
tinuing throughout the paroxysm. The small number of 
leucocytes is to be seen at the end of the paroxysm when the 
temperature is subnormal. From this time it shows a gradual 
increase until the beginning of the next attack (Billings). 

In a general way the white cells follow the same course as do 
the red. 

The differential count shows a lymphocytosis whenever the 
white cells are subnormal, the larger forms of young cells being 
especially numerous, while the adult cells and eosinophiles are 
scanty. 

In four cases of post-malarial anaemia Billings found quite 
marked leucocytosis. 

The occurrence of pigmented leucocytes has already been 
mentioned. 

Grawitz and others have noticed an increase of eosinophiles 
in post-malarial anaemia. 

FILARIA SANGUINIS HOMINIS. 

Although most commonly found in tropical countries, one 
species of this worm is not very uncommonly found in various 
l)arts of the United States. Any case of chylous urine or ele- 
phantiasis should lead us to make a careful examination of the 
blood for the filaria. There are at least four species of filaria, 
one of which is present in the blood chiefly at night, another 
chiefly during the daytime, and another continuously. Only the 
Jilaria nocfurna has thus far been seen in America (Fig. 23). 

In examining for the filaria a slide of the fresh blood is pre- 



FILARIA SANGUINIS HOMINIS. 



327 



pared m tlie usual way, hut after 8:30 o'clock in the evening,^ and 
examined at once. The embryo of this parasite (which is what 



'A 



Fig. 23. —The Filaria Sanguinis Honiinis. TIil- head, curled up, is seen at tlie riglat of the 
cut, the tail at the left. Instantaneous photomicrograph. Four hundred diameters 
magnification. 

we find in the human blood) is from one-ninetieth to one-seven- 
tieth of an inch in length, i.e., about fifty times the diameter of 





■ \- 

\ - 







Fig. 24.— Tail of Filaria, showing prolongation of nic Siieaiii oe;, ond the end of the embryo 
itself. Magnified 800 diameters. 

a red cell, and about the width of a red corpuscle. Seen in the 
blood it retains its vitality and motile power for a considerable 

' In persons who sleep in the daytime and work at night the habits of 
the filaria are said to become reversed, so that it appears in the peripheral 
circulation chiefly m the daytime, and is to be looked for then. 



328 



SPECIAL PATHOLOGY OF THE BLOOD. 



time, so that its motions may continue a week or more between 
slide and cover-glass. Cold has little effect upon it, even freez- 
ing temperature failing to do more than make the movements 
slower. 

A distinction can generally be made out between the embryo 
proper and its sheath (see Fig. 24). From this sheath the 
embryo escapes when in the blood of the mosquito, which insect 



.1 




Fig. 25.— The Movement of a Single Filaria during Four Successive Exposures of one-fifth 
of a second each, the entire series occupying less than five seconds. Magnified 800 
diameters. 

acts not infrequently as intermediary host and conveys the para- 
site indirectly from man to man through the medium of water. 
After sucking in the organism with the blood the mosquito lays 
its eggs and dies in some neighboring pond or stream whence the 
filaria again gains access to men. 

It is a long, slender, snake-like, gracefully shaped worm, and 
when alive its activity is so great that measurements and obser- 
vations of its structure cannot be made till it is paralyzed by 
approaching death (Fig. 25). 

Posteriorly it tapers for one-fifth its length down to a very 
sharp point. The extreme end of the tail often looks as if ar- 



FILARIA SANGUINIS HOMINIS. 



329 



ticulated, for it does not harmonize with the general curve of 
the body, but lies bent at an angle. Toward the head it tapers 
very slightly and when alive a " pouting" movement as if of breath- 
ing can be seen at its very extremity. About the middle of the 
body a granular aggregation can be made out along the central 
axis of the animal. Except for this granular portion the para- 
site is so translucent that it is not easy to make it out at first. 

Y^^--^—-^^— - - , ^ - 



I 



Fig. 26,— Head of Filaria. Shows structure and beginning granular degeneration. Magni- 
fied 1,500 diameters. 



The distinction of body and sheath mentioned above, appears 
as a "clear space" at each end of the body (vide Fig. 24) 
After the motions have ceased it becomes darker and traces of 
transverse striation may be seen (Fig. 26). 

It has no locomotive power and confines itself to wriggling in 
the same spot. Saussure' says he has watched them " fighting 
with each other for hours." 

The head of the filaria is said by some authorities to be sui)- 
plied with feelers or flagella, and Manson describes what he calls 
a " cephalic armature" or fang (Fig. 27) . 

1 Philadelphia Medical News, June 28th, 1890, where he reports twenty 
cases seen in Charleston, S. C. 
22 



330 



SPECIAL PATHOLOGY OF THE BLOOD. 



The same organism can sometimes be found in the chylous 
urine, but not every case of chyluria is due to the filaria san- 
guinis hominis. In a considerable proportion of cases no such 
organism is to be found. 

Henry {Med. Neivs, May 2d, 1896) succeeded in staining the 
parasites intra vitam by giving the patient considerable doses 
of methylene blue internally for some weeks. Only a faint 




Fig. 27.— Head of Filaria Magnified 1,500 Diameters. The blur in front of the head may be 
due to the motion of fiagella. 



bluish tinge was imparted, however, to the organism by this 
method. 

For finding the parasite it is best to use a low power, not an 
immersion lens, and the whole of several slides should be looked 
over. 

Specimens can be dried and preserved for staining provided 
we do not heat them over a lamp or pass them through a flame. 
Manson^ stains with eosin and mounts in " glycerin jelly" (Fig. 
*J8). 

Several other species have been observed in England in 

' The "Filaria Sanguinis Hominis," by Patrick Manson, M.D., Amoy, 
China, 1883. 



SPIROCHETE OF RELAPSING FEVER. 



331 



negroes from the Congo Eiver, but not hitherto in America. 
But as it frequently is to be found in persons who have no 
symptoms whatever, it may well be that some of these other 
species would be found here if one took the trouble to seek out 
natives of Southern China (one out of every ten of whom carries 




i 1 

I 

i ■ . 



L_--^-ak!kk . „ -.- --^ 

Fig. 28.— Head of Filaria Overlapping a livd cN.rpuscle. The api>eai'auce ungiit be mis- 
taken for the cephalic end of a sheath. 

about the filaria in his blood), or of Central Africa, or other 
tropical regions. 

SPIROCHETE OF RELAPSING FEVER. 

During the febrile paroxysms of relapsing fever, and for 
one or two days before them, Obermeyer and others have found 
constantly present in the peripheral circulation a parasite whose 
length averages about six times the diameter of a red corpuscle. 
Even under high-power lenses it is a mere thread in width, 
curled upon itself like a corkscrew and actively motile, so that 
in examining the blood with a low power we get " a peculiar 
impression of disturbance" among the red cells. 

The number of twists in this spiral-shaped organism varies 
a good deal, and one of its motions consists in contracting and 
extending itself like a spiral spring. It can thus multiply its 
own length three or four times. It has also a delicate, wavy, but 
rapid motion along its long axis. The whole thread, or a part 
of it only, may have these motions. Further, the whole parasite 
has power of locomotion apparently independent of the currents 



332 



SPECIAL PATHOLOGY OF THE BLOOD. 



in the blood plasma of a slide and cover-glass specimen. Its 
locomotion is slow compared to the movements above described. 
Particularly in the blood post mortem they are apt to wind 
themselves into each other so as to seem much larger than they 
actually are, and sometimes a large " nest" of them may look 
like a leucocj^te, except for the fine, wavy threads which can 
be seen in motion at the periphery of the mass. 

The number present in the blood is very much smaller at the 
beginning of a paroxysm than after the second day. During the 
first few hours of a febrile period Mocyntkowsky could find only 
one spirochaete in ten or twenty microscoi^ic fields, while later 
on he saw twenty or thirty of them in a single field. There are 
usually more parasites with each successive paroxysm. 

Blood taken from "different parts of the body often shows a 
great difference in the number of organisms to be found. The 
life history of a single parasite seems to be very short, but they 
multiply with the greatest rapidity. Albrecht has seen them so 
increase within six hours that whereas at first he saw only a 
few in the whole slide he later found many in each field. As 
the spirochaete dies, its movements get languid and finally it 
breaks up into small granular bits (spores?). 

Between paroxysms the spirochsetes are not found, but there 
are to be seen peculiar highly refractile globules compared by 
V. Jaksch to a diplococcus. The latter author believes that he 
has seen these develop into the spirochsete at the beginning of 
a paroxysm and hence believes them to be spores. 

This spirochaete is found in all cases of relapsing fever and 
in no other known disease, so that like the Plasmodium malariae 
it is pathognomonic and of the highest importance. 

Anaemia and leucocytosis are among the secondary results of 
the presence of this parasite in the blood. 

A certain resemblance has been noted between the spirochaete 
and a free flagellum broken off from a malarial parasite, but the 
clinical history and the presence or absence of other evidence of 
malaria in the blood would easily decide the question of diag- 
nosis. 

TecJinique of Examination. — As in looking for the malarial 
organism it is best to examine the blood fresh between a slide 
and cover-glass (vide supra, page 7) and to use an oil immer- 
sion lens. In dried specimens the organism can be stained 



ANEMIA DUE TO INTESTINAL PARASITES. 



333 



with fuclisiu, but it is much more difficult to recognize than in 
the fresh blood. 

DISTOMUM H^MATOBIUM. 

Bilharz found this parasite post mortem in the large internal 
veins (portal, splenic, mesenteric, etc.), but as it has never been 
seen in the peripheral circulation its clinical importance is thus 
far nil. 

BACTERIA IN THE BLOOD. 

(a) Cover-Glass Specimens. — Bacilli of anthrax, tuberculosis, 
glanders, grippe, typhoid fever, and tetanus have been demon- 
strated in the blood of human beings as well as have the pyo- 
genic streptococci and staphylococci, the diplococcus lanceolatus, 
the gonococcus, and the bacillus coli communis. Nevertheless it 
is exceedingly difficult and frequently impossible to find them, 
and no considerable practical use has as yet been made of the 
cover-slip examination of blood for micro-organisms. 

Gunther's method is an excellent one. Cover-glass speci- 
mens of the blood are prepared as above described (page 32), 
and left a few seconds in five-per-cent acetic acid to render the 
red cells invisible ; the acetic acid is then shaken {not ivasJied) off 
and the cover-glass held over the mouth of a bottle of strong 
ammonia water to neutralize the remaining acid. The covers 
are then stained with the Ehrlich-Weigert solution,' mounted in 
balsam, and examined with a one-twelfth immersion lens. 

ih) Cultures (see above, page 35). 

AM^MIA DUE TO INTESTINAL PARASITES. 

The bothriocephalus latus, ankylostoma duodenale, and a 
few other parasites are capable of producing by their presence 
in the intestine a very severe anaemia, which may be indistin- 
guishable from pernicious anaemia. As yet no such case has 
been reported in this country, but Askanazy'^ and Schaumann^ 

^ To 6 c.c. of distilled water add ten drops of aniline oil and filter. To 
the filtrate add a saturated alcoholic solution of gentian violet till slight 
(transient) turbidity appears. On the surface of this solution in a watch 
glass float the cover-glass face downward for twenty-four hours. 

2 Vereins-Beilage der Deut. med. Woch., 1895, Bd. 148. 

3 " Bothriocephalus-Anaemia, " Berlin, 1894 (Hirschwald). 



334 



SPECIAL PATHOLOGY OF THE BLOOD. 



have carefully studied the disease in Germany and found that 
the blood may correspond exactly with that of pernicious anae- 
mia, including the presence of high color index and of a major- 
ity of megaloblasts among the nucleated red cells present. Yet 
such cases may be rapidly and permanently cured by expelling 
the parasites from the intestine. No special descrij^tion of the 
blood states need be given, as they present nothing peculiar. 



CHAPTEE XII. 



THE BLOOD IN INFANCY. 

I. All the signs hy luMch sickness is shown in the blood of adults 
are exaggerated in children. Their blood is apparently more 
sensitive to the action of any morbid influence. Causes leading 
to but slight anaemia or leucocytosis in the adult, produce grave 
anaemia and very marked leucocytosis in children. Into the 
reasons for this I shall not attempt to enter. The increased 
toxicity of their serum compared to that of adults, and the rela- 
tively recent establishment of the functions for producing and 
destroying blood have been suggested as explanation. 

Comparatively slight hemorrhages, gastro-intestinal or re- 
spiratory disorders, which would not impoverish an adult's blood 
may produce considerable anaemia in a young child. 

II. All forms of anaemia in infancy are apt to be associated 
with enlarged spleen. 

III. I have already alluded to the polycythaemia and leucocy- 
tosis of the new-born, and the gradual fading out of these rela- 
tive abnormalities as the child grows up. In judgments as to 
the presence or absence of leucocytosis in infancy, these physio- 
logical variations are too often lost sight of, especially as the 
proper leucocyte count for any given infant depends not simply 
on its age but on the backwardness or forwardness of its develop- 
ment. As with the fontanelles, the growth of the blood toward 
adult conditions may be retarded by congenital weakness (infan- 
tile atrophy, marasmus) or inherited disease (tuberculosis, syph- 
ilis) as well as by acquired sickness (rickets, cholera infantum). 

Under the influence of any of these drawbacks a sick child's 
blood may be no further developed* at three years than that of a 
healthy child of eighteen months. 

IV. When we remember that in early infancy the leucocytes 
differ from those of adults not only in number but in that the 
young leucocytes are relatively more numerous ("lymphocytosis 
of infancy"), we shall understand that any influence like rickets 



336 



SPECIAL PATHOLOGY OF THE BLOOD. 



or syphilis which retards development, will show lymiDhocytosis 
together with the increased leucocyte count. Qualitatively as 
well as quantitatively the blood reverts to a more infantile con- 
dition. 

V. This shows itself not merely in the leucocytes but in the 
red corpuscles. During the first days after birth the infant's 
blood shov\'S greater variations in size and shape than that of 
-adults, as if the type were not yet quite fixed. The majority of 
authors also find a few normoblasts in the first few days of life. 
These are not invariably present, doubtless because in some 
children the blood at the time of birth is more developed than 
in others. 

Under pathological conditions the red cells revert to this 
earlier type and deformed or nucleated corpuscles are plentiful. 
This is more marked than in anaemia of the same grade oc- 
curring in adults. An anaemia that shows but thirty nucleated 
erythrocytes per cubic millimetre in an adult might show ten 
times that number in a child. 

YI. As, we said before, all blood changes are exaggerated in 
infancy. This includes such physiological changes as the diges- 
tion leucocytosis or that following cold bathing as well as patho- 
logical leucocytosis and anaemia, and changes in the degree of 
dilution or concentration of the blood seem to be similarly exag- 
gerated, as is seen, e.g., in the x>hysiological variations in the 
specific gravity of the serum (Hock and Schlesinger') . 

YII. The hcemoglobin , though relatively high at birth and 
for the first few weeks, is lower than that of adults during 
the rest of childhood. The high percentages of the earliest 
weeks are not due to a polycythsemia, but to a genuine in- 
crease of haemoglobin in the individual cells (Schiff^), color 
indexes being often over 1. 

It is indispensable, therefore, that we should know the age 
and degree of development of a child before we can draw accurate 
inferences from its blood. In many of the cases reported in lit- 
erature we are unable to judge whether the blood condition is 
pathological or not, because the age of the child is not given. 
Tor example, v. Limbeck' quotes a case of acute gastritis re- 

1 Hock and Schlesinger Centralb. f. klin. Med., 1891. 

2 Schife: Zeit. f. Heilk., vol. xi., 1890. 
^ V. Limbeck: loc. cit., p. 373. 



THE ANEMIAS OF INFANC?'. 



337 



ported by Fisclil ' as Laving an unusually high percentage of 
young leucocytes (59.4 per cent). But this is physiological in 
the first days of life and may have been so in this case, the age 
not being given. 

Observations of this sort should always represent a compari- 
son between the conditions present before and during the sick- 
ness in question. 

Bearing these general considerations in mind, we shall be 
better able to find our way among the complications and per- 
plexities of the blood conditions in infancy. 

THE ANEMIAS OF INFANCY. 

As above mentioned, anaemic infants are apt to have enlarged 
spleens. This may be due either to the anaemia or to some 
disease accompanying or underlying the anaemia {e.g., rickets, 
syphilis). It seems more probable that the hypertrophy is not 
directly or exclusively dependent on the anaemia, inasmuch as 
similar blood changes are found without splenic enlargement. 
By far the greater number of reported cases of severe infantile 
anaemia are accompanied or caused by such diseases as rickets 
and hereditary syphilis, both of which may cause splenic hy- 
perplasia even when no anaemia is present. It seems probable 
that the anaemia and the enlargement of the spleen are alike 
symptomatic of an underlying disorder. 

1. Some writers {e.g., Luzet^) divide the anaemias of infancj^ 
into two classes : those with splenic enlargement and those with- 
out it. Luzet considers that the former class is severer than 
the latter and more apt to show large numbers of nucleated red 
corpuscles than those with normal-sized spleens. This classi- 
fication, however, does not always hold. "We may have very 
severe anaemia without splenic enlargement and splenic en- 
largement with slight anaemia,, and the presence or absence of 
numerous nucleated red corpuscles is governed by conditions 
other than the size of the spleen. 

2. Another classification of children's anaemias was proposed 
in 1892 by Monti and Berggriin (" Die clironische Anamie im 
Kindesalter, " Leipzig, 1892). They divided the cases into 



^ Fischl : Zeit. f. Heilk., 1892. ^ L^zet : Diss,, Paris, 1891. 



338 



SPECIAL PATHOLOGY OF THE BLOOD. 



the mild and the grave, each group being subdivided into those 
with leucocytosis and those without it. 



They rightly discard the term " splenic anaemia," correspond- 
ing as it does to no single set of blood changes. The above 
classification puts pernicious anaemia, leukaemia, and anaemia 
infantum pseudoleukaemica (v. Jaksch) in a different category. 

(a) Mild cases of secondary anaemia show no deformities in 
the shape or size of the red cells. The color index may or may 
not be low. The cases with leucocytosis are much more numer- 
ous than those without it and more apt to have a low color index ; 
in other words, the loss of corpuscle substance is greater and 
the cases are approaching the imaginary boundary between 
"mild" and "grave." 

{h) The grave cases have poikilocytosis, and of course a 
greater reduction of corpuscle substance. 

" Chlorotic" conditions, and most but not all those with en- 
larged spleen, come under this heading ; also most of those due 
to hereditary syphilis, prolonged diarrhoea, and rickets. 

In 1894 Monti ' gave the following classified lists of the com- 
monest antecedents of secondary anaemia in infancy : 



Secondary anaemia of infancy = 




_ ) Witii leucocytosis. 
■~ ( Without leucocytosis. 





' 1. Hemorrhage. 




Scurvy, purpura, haemophilia, Werl- 



3. Acquired . . 



^ 2. Other causes. 



f Inanition. 
Bad hygiene (lack of light, air, etc.). 
Post-febrile. 

Nephritis, diarrhoea, serous effusions. 
<J Syphilis. 
Rickets. 
Suppuration. 

Diseases of liver, spleen, bone, or 



lymph glands. 



He points out that cases with leucocytosis are usually graver 
than those without it and may develop into pernicious anaemia ; 
1 Wiener med. Woch., 1894. 



THE ANEMIAS OF INFANCY. 



339 



also that the presence of leucocytosis does not point to malig- 
nant disease, suppuration, or any of the causes which usually 
account for it in adults. 

Grave cases with leucocytosis in infants under twelve months 
are apt to develop into the anaemia infantum pseudoleukaemica, 
or into true leukaemia or pernicious anaemia. 

On the whole, the division of Monti and Berggriin seems 
much better than that according to the particular causes, e.g., 
"rachitic anaemia," "syphilitic anaemia," etc., for there is no 
particular set of blood changes that follows rickets, syphilis, or 
any other disease. In connection with various diseases of in- 
fancy, and particularly with those last named, we may have 
anaemia of any grade of severity from that reducing the red 
cells to 4,000,000 down to cases with only 500,000 red cells per 
cubic millimetre or even less. The worse the case is the more 
likely is it to be accompanied by leucocytosis and the more nu- 
merous will be the nucleated red corpuscles, always more numer- 
ous here than in anaemia of adults. 

In syphilis, hereditary or acquired, the red cells may fall be- 
low 1,000,000 and the leucocytes may rise as high as 58,000 
(Loos). The haemoglobin may be proportionally diminished, 
or may be even lower than the percentage of red cells, so that a 
" chlorotic" condition obtains. 

Such cases have been called chlorosis, but it seems better to 
confine this term to anaemia of unknown origin and favorable 
course occurring in women soon after puberty, since obviously 
secondarj^ cases may have similar blood. 

Rickets in a case observed by v. Jaksch caused a fall of the 
red cells to 750,000 and Luzet counted 1,590,000 in a similar 
case. The haemoglobin is usually low, but Hock and Schles- 
inger found 60 per cent with 2,300,000 red cell, a color index of 
1.2 +. 

Leucocytosis may occur even when no anaemia is present. 
Hock and Schlesinger found 45,000 leucocytes in a rachitic child 
of sixteen months, sound in other respects and not anaemic. 
Acute gastritis causes at first only leucocytosis (with increased 
percentage of young forms). If it becomes chronic the reduction 
of red cells is severe. Hay em found only 685,000 red cells per 
cubic millimetre in an infant of two months, though recovery 
eventually took place. 



340 



SPECIAL PATHOLOGY OF THE BLOOD. 



In tuberculosis of luugs aud peritoneum in a child of seven, 
Monti and Berggriin counted 3,230,000 red and 17,200 white 
cells with 52 per cent of haemoglobin. 

Qualitative Changes. 

The exaggeration characteristic of all blood changes in in- 
fancy extends to the presence of nucleated red corpuscles, which 
in all forms of severe ansemia are very numerous. What has 
been described above (page 76) as the typical megaloblast, a 
large pale-stained nucleus in a very large cell (see Plate lY.), is 
relatively rare in infancy. The nuclei are almost always deeply 
stained whatever their size, aud apt to be small. Dividing 
nuclei are very common, both by karyolysis and karyokinesis. 
These changes are most often found in the anaemias of the 
severest type and those which resemble leukaemia (see below, 
page 346) , but may occur in any marked secondary anaemia. 
Polychromatophilic and " degenerative" changes are very com- 
mon in severe cases. 

The increased leucocyte count, so frequently fouud, is often 
made uxj of a majority of the young forms (lymphocytes). This 
change, as above said, is not characteristic of rickets, syphilis, 
or any other cause of anaemia, but is to be regarded as a mark 
of the arrest of development or reversion to an earlier type of 
tissues brought about by various diseases in early infancy. 
Sometimes the large lymphocytes and sometimes the small are 
in excess. 

A further qualitative change already alluded to (see above, 
page 104) is the occurrence of myelocytes. We have seen that 
small percentages of these cells are not uncommonly seen in the 
anaemias of adults. Now this, like all other blood changes, is 
exaggerated in infancy. Myelocytes are more apt to appear and 
in greater numbers. Their presence is not characteristic of any 
one disease, but they are commonest in the severer types of 
secondary anaemia, such as those following syphilis and 
rickets. Their significance is about the same as that of nor- 
moblasts. At times, however, they are so numerous as to 
make us hesitate somewhat before we exclude splenic-myelo- 
genous leukaemia. 

This brings us naturally to the discussion of the ditficuJtii of 
distinguishing the different blood diseases in infancy, which natur- 



"anemia infantum pseudoleuk^mica." 341 

ally centres in the question of the existence and nature of the 
so called 

"ANEMIA infantum PSEUDOLEUK^MICA." 

Yon Jaksch's' decription of this disease (which he was the 
first to recognize) includes the following elements : 

1. Grave anaemia — e.g., 820,000 red cells per cubic millimetre 
in one case. 

2. Extensive leucocytosis — e.g., 54,660 white cells per cubic 
millmetre, in the same case. 

3. Great variations in the form, size, and staining of the 
white cells. 

4. Deformed, degenerated, and nucleated red cells. 

Von Jaksch admits that none of these blood changes are 
characteristic of the disease, but thinks that its title to the posi- 
tion of a distinct and separate disease rests upon clinical data, 
the more important of which are : (1) A great enlargement of 
the spleen without any such accompanying enlargement of the 
liver as is usually found in leukaemia (the lymph glands are 
sometimes enlarged). (2) A relatively good prognosis. (3) Post 
mortem we find no positive evidence of leukaemia. 

This description was given by v. Jaskch' in 1889. He stated 
the relation of white to red corpuscles as 1 : 12, 1 : 17, and 1 : 20 
in the cases seen by him. Later he rejjorted three cases in one 
of which the white cells numbered 114,150, and the red 1,380,- 
000. The differential counts are not carefully given. 

Almost at the same time Hayem' reported a similar case, 
and noted the abundance of nucleated red corpuscles many of 
which were undergoing mitosis. This was verified by Luzet ^ 
in May, 1891 {Arch. gen. de 3Ied.), who reported two cases. 
His description of the disease differs considerably from that of 
V. Jaksch. He finds no greater difference between liver and 
spleen than often exists in true leukaemia. The course of the 
disease, though sometimes chronic, usually ends in death. The 
leucocytosis in Luzet' s cases was less marked than in those of v. 
Jaksch and not greater than that occurring in many anaemias 
of children. He dwells particularly on the large number of nu- 

' Von Jaksch: Wien. klin. Woch., 1889, Nos. 22, 23. 

2 Hayem . Gaz. des Hopitaux, 1889, No. 30. 

3 Luzet : Diss., Paris, 1891. 



342 



SPECIAL PATHOLOGY OF THE BLOOD. 



cleated red cells, and the frequency of mitosis and considers tMs 
the most important diagnostic point. 

Although Luzet's continues to use the name suggested by v. 
Jaksch, he describes the disease so differently that it is difficult 
to see why the same title should be given to it. He agrees with 
V. Jaksch in thinking that it is not simply a severe secondary anae- 
mia due to sj^philis, rickets, tuberculosis, or infectious disease. 

Somewhat similar cases had already been described by vari- 
ous Italian writers {e.g., Fede) under the title of "Infective 
Splenic Ancemia of Infants.'' 

Among others who have written on the subject are Baginsky,^ 
Senator, " Fischl,^ Andeoud,' Monti and Berggriin,' Felsenthal,^ 
Eaudnitz,' Epstein," Alt and Weiss," Hock and Schlesinger,'" 
Crocq,'' and Kotch.'^ 

The majority of these writers report very little as to the dif- 
ferential counts of white corpuscles. An increased percentage 
of the adult forms is mentioned by many, but Kotch in a case 
with 1,311,250 red cells and 116,500 white cells found only 16 
per cent of the adult variety with 46 per cent of small lymx)ho- 
cytes, 34 per cent of large lymphocytes, and 4 per cent eosino- 
philes. A second case had only 14 per cent of adult cells and 
84 per cent of lymphocytes (large and small). 

Von Jaksch noted the lack of any relative increase of eosino- 
philes, supposing this to be a means of distinguishing his cases 
from true leukaemia. Luzet, on the other hand, found eosino- 
philes numerous. (This of course has no weight for or against 
leukaemia. ) 

Klein (loc. cit.) noted the occurrence of myelocytes in small 
number. 

^ Baginsky : Arch. f. Kiuderheilk., 1892, vol. 13. 
5 Senator: Berlin, klin. Woch., 1892. 
3 Fischl : loc. cit. 

* Andeoud : Rev. de med. de la Suisse rom., 1894, p. 507. 
^ Monti and Berggriin : loc. cit. 
^ Felseuthal : loc. cit. 

'Raudnitz: Prag. med. Woch., 1894, p. 6. 

8 Epstein: Prag. med. Woch., 1894, p. 6. 

^ Alt and Weiss: Centralb. f. med. Wissenschaft, 1893. 

^0 Hock and Schlesinger : loc. cit. 

" Crocq: " Etude sur 1' Adenie, etc. , Brussels, 1891 (Lamaitin). 
^- Rotch : Paediatrics, 1895, p. 361. 



"anemia infantum pseudoleuk^mica." 



343 



The discrepancy of these different reports is suggestive. 

The chief importance of the heterogeneous group of cases 
which have received the name of ancemia infantum pseudoleu- 
'kcemica seems to me to be as a proof of the difficulty of distin- 
guishing the various blood diseases in infancy. 

Among the cases reported under this name are some which 
might be any one of the following list: Pernicious ansemia, 
secondary anaemia with leucocytosis, Hodgkin's disease, lym- 
phatic leuksemia, and probably splenic-myelogenous leukaemia. 

(a) Most of the few reported cases of pernicious anaemia in 
infancy have shown moderate leucocytosis (as compared with 
adult blood), a fact which deprives us of one of the means of dis- 
tinguishing the disease from secondary anaemia. The reports 
as to nucleated corpuscles very rarely separate normoblasts from 
megaloblasts, and we have no way, therefore, of being sure on 
this important point. The high color index and large diameter 
of the red cells are occasionally seen in other anaemias of infancy 
and are not always present in pernicious cases. The great 
fatality of all kinds of anaemia in infancy prevents our calling a 
cd^^Q pernicious because of a fatal termination. Enlargements of 
liver and spleen occur in many cases of each type of infantile 
anaemia, and occasionally in pernicious anaemia of adults. They 
do not, therefore, exclude pernicious anaemia in infancy. 

Bearing these facts in mind, it is evident that some of Luzet's 
cases of "anaemia infantum pseudoleukaemica" may have been 
pernicious anaemia. "Von Jaksch's own cases may have been 
either {a) Hodgkin's disease with leucocytosis, (b) grave secon- 
dary anaemia with leucocytosis (Monti and Berggriin), or (c) 
leukaemia. 

(a) Hodgkin's disease, which v. Limbeck finds to be very 
common in infancy, may affect the liver and spleen and not the 
external lymph glands, and maj^ be accompanied by anaemia 
and leucocytosis such as v. Jaksch describes. Epstein con- 
siders that this is the case, and denies the existence of anj' such 
disease as the anaemia infantum pseudoleukaemica. 

(b) As any anaemia secondary to rickets or syphilis may have 
enlarged spleen and liver and marked leucocytosis, we cannot 
tell from v. Jaksch's description that we are not dealing in his 
cases with secondary anaemia. 

(c) Since v. Jaksch does not give any accurate differential 



3U 



SPECIAL PATHOLOGY OP THE BLOOD. 



count of the leucocytes, there may have been large numbers of 
myelocytes in his cases for all we know, or an overwhelming 
percentage of lymphocytes, i.e., either type of leukaemia. 

One of the cases reported by Eotch as " anaemia infantum 
pseudoleukaemica" had 80 per cent of lymphocytes in a leucocyte 
count of 116,500, the ratio of white to red cells being 1 : 11, and 
the nucleated corpuscles abundant. The external lymph glands 
as well as the liver and spleen were enlarged. How such a case 
is to be distinguished from lymphatic leukaemia without autopsy 
I cannot see. Large numbers of nucleated corpuscles with mito- 
ses (present in this case) are to be found in any anaemia of in- 
fancy where the red cells, as in this case, have sunk as low as 
1,311,500, and therefore do not exclude leukaemia. 

Yon Jaksch protests that his cases are not secondary to 
rickets or any other disease, but Fisclil ' in a careful study of all 
the published cases finds that out of a total of eighteen cases, 
sixteen had severe rickets 'and tAvo hereditary syphilis. 

The writings of Kaudnitz, Ebstein, Telsenthal, Fischl, and 
V. Limbeck, which deny the separate existence of the anaemia 
infantum pseudoleukaemica, are convincing to me, and are rein- 
forced by the few cases of bad anaemia in children which I have 
seen. We must distribute the cases of anaemia with leucocy- 
tosis and large spleen under pernicious anaemia, secondary an- 
aemia, and leukaemia. 

But our problem is not yet nearly solved. All we have 
gained is the belief that v. Jaksch 's new disease does not help us 
to classify these doubtful cases. The difficulty is still very great. 
The following case illustrates this : 

A male child of sixteen months with symptoms of grave 
anaemia, greatly enlarged spleen and slightly enlarged liver, 
showed the following figures: Eed cells, 2,500,000; white cells, 
22,000. Differential count of 500 cells showed: Young cells, 
53.8 per cent (46.2 of the smaller type); adult cells, 29.4 per 
cent; eosinophiles, 6.2 per cent; myelocytes, 10 per cent. 

While counting these, 147 nucleated red corpuscles were seen, 
of which 21 were normoblasts, 50 megaloblasts, and 47 micro- 
blasts; 6 showed mitosis in their nuclei. 

The child died shortly after without any complication or 
intercurrent disease. No autopsy. No evidence of rickets or 
syphilis or other previous disease. 



J Fischl : Zeit. f. Heilkunde. 1892. 



"ANEMIA INFANTUM PSEUDOLEUK^MICA." 345 

Now I see uo reason for supposing this to represent a new 
type of anaemia, and yet I cannot feel perfectly safe in classify- 
ing it as primary anaemia, secondary anaemia, or leukaemia. 

(a) Primary or pernicious anaemia should have a lower count 
of red cells and a majority of megaloblasts. The percentage of 
myelocytes (ten per cent) is higher than in any other case of 
pernicious anaemia on record, though in one adult case w^ith au- 
topsy I found 9.2 per cent with a leucocytosis of 12,500, or 1,- 
150 myelocytes per cubic millimetre, against 2,200 per cubic 
millimetre in this case. 

(h) It is hard to call an anaemia secondary which kills with 
no complications and when there is no evidence of any disease 
to which it can be secondary. 

(c) For splenic-myelogenous leukaemia the total leucocyte 
count and the percentage of myelocytes are very small. Still the 
leucocyte count may drop very low in leukaemia even without 
any inflammatory complication. Such a case is reported by 
Osier, in which the leucocytes fell to 7,500, of which only 300, 
or four per cent, were myelocytes. 

Hay em (he. ext., page 864) in a ten months' child counted 
2,712,500 red and 33,000 white cells, almost the same figures 
as in the case just quoted. [Hayem unfortunately gives no 
differential count, but apparently considers the case leukaemic 
because of the enormous number of nucleated red cells, many 
with mitoses.] 

Morse's case of leukaemia in infancy had 2,900,000 red and 
48,000 white cells. Twenty-one and four-tenths per cent of the 
leucocytes, or about 10,000, were myelocytes. The same abun- 
dance of nucleated red cells (some with mitoses) were here pres- 
ent as in Hay em's case, so that there is evidently nothing pecu- 
liar in their presence in the disease described by v. J aksch, as 
Luzet supposed. 

These cases show that leukaemia may at certain periods pre- 
sent just such a blood picture as was present in the above-quoted 
case and that the number of leucocytes in the leukaemia of in- 
fants may be no greater than that in any anaemia with the leu- 
cocytosis so common in children. 

It seems to me the most natural conclusion to be deduced 
from these facts is that we meet with cases in infancy loliich are 
appai^ently intermediate hetioeen leukcemia and pernicious ancemia. 
23 



3i6 



SPECIAL PATHOLOGY OF THE BLOOD. 



I have pointed out elsewhere that there are many points of re- 
semblance between the two diseases. The case of lenktemia re- 
ported bv Osier showed at one period — the period of remis- 
sion — a fall in the number of leucocytes and in the percentage 
of myelocytes till the blood was practically that of pernicious 
anfemia. 

Dr. Eotch's case (above quoted) is another in which the diag- 
nosis seems to lie somewhere intermediate between the two 
diseases, anaemia and leukaemia. 

The case which I have quoted above seems to me on the 
whole nearer to the type of x^ernicicus anaemia than of leukEemia, 
and Dr. Eotch's nearer to the latter than to the former; but each 
is really intermediate, so jar as the Hood gots, between the two 
diseases. I have no intention of suggesting that the organic 
lesions in these cases are intermediate between leukaemia- and 
pernicious antemia. It is simply the blood that is so. 

Engel's case, reported in Yirchow's ArcJiiv, Vol. 135, sug- 
gests the same thing. He calls the case one of " pseudo-pemi' 
cious ancemia.''' Meylocytes were abundant. 

Polymorphous Condition. 

This illustrates that " polymorphous" condition of the blood 
^hich V. Jaksch supposed to be characteristic of the ansemia in- 
fantum pseudoleukaemica. The same thing was very marked in 
all the bad cases of anaemia which I have seen, including 
the case above mentioned, and a case of true leukaemia in 
a girl of eight. The impression one gets from the field of a 
stained specimen is that no two ichite corpuscles are alike. Every 
species is subdivided into several sub-varieties and all stages of 
degeneration are to be seen in each variety. But this is char- 
acteristic of any very severe infantile anaemia and not of any 
single type. 

LErEL5:MIA. 

In Morse's careful article of August, 1894 {Boston Med. and 
Surg. Journal), twenty cases of leukaemia in infancy are collected. 
As he rightly says, probably most of these cases were not gen- 
uine. Only one of them includes a differential count, and this is 
in a lymphatic case. Morse's is the only one of the splenic- 



LEUKAEMIA. 



347 



mj^elogenous type on record in wliicli the diagnosis is made 
reasonably certain by a color analysis. Fisclil in 1892 said 
that there was no case on record with a differential count. It 
seems to be actually the case, therefore, that we have only two 
genuine cases of leukaemia in infancy from which to generalize, 
both occurring in the practice of Boston physicians. 

The first case, seen in 1890 by Dr. F. C. Shattuck, was 
apparently acute, the symptoms appearing only six weeks be- 
fore death. Cover -glass preparations examined by W. S. 
Thayer showed a ratio of about 1 white to 20 red cells. The 
differential count' showed: Small lymphcocytes, 97.9 per 
cent; large lymphocytes, .7 per cent; "polynuclear" cells, 1.4 
percent; eosinophiles, .08 per cent. 

The other case reported by Morse has been mentioned above. 
No generalization is possible until other cases shall be added to 
these. 

^ Reported by Thayer in the Boston Medical and Surgical Journal, 
1893, vol. 138, p. 183. 



PART VII. 

EXAMINATION OF THE SERUM. 



CHAPTER XIII. 

THE CLUMP REACTION. 

Geneeal Description. 

Although tliis phenomenon is to be obtained in various in- 
fections, natural as well as experimental, and with, various body 
fluids, I shall describe as a typical case of it the reaction which 
takes place when the blood serum of a patient ill with typhoid 
fever is added in certain proportions (vide infra) to a young 
bullion culture of well-certified and virulent typhoid bacilli. In 
a drop of such a mixture, examined between slide and cover- 
glass^ with a magnification of 300 diameters or more (an immer- 
sion lens is not necessary) , we notice, as soon as the serum and 
culture are mixed, either a marked slowing of the progressive 
movements of the bacilli or an unequal distribution of them in 
the different parts of the preparation, some parts showing the 
bacilli closely crowded, while in others they are more scat- 
tered. Whichever of these changes occurs first, the slowing of 
locomotion or the tendency to grouping, the other soon follows, 
and then both processes go on together, as admirably described 
by Biggs and Park : ^ 

" Some of the bacilli soon cease all progressive movement, 
and it will be seen that they are gathering together in small 
groups of two or more, the individual bacilli being still some- 
what separated from each other. Gradually they close up the 
spaces between them, and clumps are formed. According to the 

' Hanging-drop preparations are often recommended, but a simple slide 
and cover-glass are as good for the purposes of this reaction. 
2 American Journal of the Medical Sciences, March, 1897. 



THE CLUMP REACTION. 



349 



completeness of the reaction, either all the bacilli may finally 
become clumped and immobilized or only a small portion of 
them, the rest remaining freely motile, and even those clumped 
may appear to be struggling for freedom. With blood contain- 
ing a large amount of the agglutinating substances all gradations 




Fig. 30.— Partial Reaction. Fig. 31.— Typical Clumping. 



in the intensity of the reaction may be observed, from those 
shown in a marked and immediate reaction to those appearing 
in a. late and indefinite one, by simply varying the proportion of 
blood added to the culture fluid" (see Figs. 29, 30, and 31). 

The process may go on gradually and be much more distinct 
at the end of half an hour. 

The groups or clumps above described constitute the impor- 
tant part of the reaction for diagnostic purposes. Of the loss of 
motility more v^ill be said later. 



350 



SPECIAL PATHOLOGY OF THE BLOOD. 



The clumps may hang together for a long time. They have 
been observed unchanged for one hundred and forty -four hours. 
On the other hand, they may be dissolved in a few hours and the 
bacilli regain their motility. 

In watching the formation of the clumps it is easy to see 
that the bacilli are positively attracted to each other and do not 
drift passivel}' into a heap. The loss of motility is not the 
cause of the clumping, as they often begin to approach each 
other while in vigorous motion. The power of locomotion is 
lost much sooner than are the squirming and spinning motions, 
which often persist among the bacilli in the peripheral parts of 
the clumps as well as outside them. 

The clumps tend to adhere to the under side of the cover- 
glass. 

Specimens can be fixed and stained with the bacilli in clumps 
— contrasting strongly with the even distribution of the bacilli 
in ordinary stained preparations. 

Technique of the Clump Eeaction in Typhoid Fevee. 

Our account of the methods of obtaining the clump reaction 
may be divided into the following parts : 

1. The body fluids to be used and the methods of obtaining 
them. 

2. The cultures. 

3. Dilution and the time limit. 

1. The Body Fluids to be Used. 

Experiments have proved that the reaction can be obtained 
with the following fluids : 

(a) The whole blood, fluid or dried. 

(b) The plasma and serum, fluid or dried. 

(c) The fluid obtained by blistering. 

(d) The fluid normally present in the pericardium, pleura, 
peritoneum, and joints; not in rapidly accumulated effusions. 

(e) The milk and colostrum of women suffering from typhoid 
during lactation. 

(/) Pus from persons suffering with typhoid — whether the 
bacilli of Eberth are present in the pus or not. 



THE CLUMP REACTION. 



351 



((/) Tears — naturally {i.e,, gradually) secreted. If secreted 
in response to the irritation of ammonia fumes, tlie tears do not 
produce clumping. 

(Ii) Some observers also find it in the fluid of oedema and in 
the bile. Others do not. 

(i) The clumping persists in the above-named fluids after 
death and even in putrefaction. The "juice" of the spleen,, 
kidneys, and rarely of the liver, will give the reaction feebly. 

{j) Though present in the placental blood of pregnant 
typhoid patients, it does not usually exist in the foetus. 

The saliva, gastric juice, and sweat do not produce the reac- 
tion, so far as known. The aqueous humor sometimes does. 

The urine and fgeces sometimes do and sometimes do not give 
it, but these excretions in normal persons may also produce the 
reaction, so that they cannot be made clinically available. 

Of all these fluids, the blood, the serum, and the fluid of 
blisters are the only ones used in clinical work, both because 
of their greater convenience, and because the clumping power is 
much more marked in the blood and blister fluid than in any of 
the others. 

1. Use of the Wliole Blood — Fluid. 

Tlie advantages of this method are {a) its quickness, and (6) 
the small amount of blood {one dvop) sufficient for the test. 

Its disadvantages are (a) that the corpuscles interfere slightly 
with the fields in which the reaction is to be watched, and (5) 
that they sometimes lead to the formation of false clumps 
(" pseudo-amas") , which simulate those present in the real 
clump reaction, and lead to false inferences. Both these objec- 
tions are trifling, however, as the corpuscles can be excluded by 
waiting a minute or two until they settle, leaving a clear liquid 
above in which the reaction can be observed. The false clumps 
are rarely seen, and can be differentiated from the true by care- 
ful technique (see below). 

I have used this method in many cases and always found 
it satisfactory and convenient. Widal, McWeeney, Delepine, 
and Coleman have employed it with success. It is most suit- 
able for the "quick method" (see page 355), and is chiefly em- 
ployed in this way. 

Procedure. — Suck up some water with a medicine-dropper and 



352 



SPECIAL PATHOLOGY OF THE BLOOD. 



expel ten drops of it into a watch-glass. Then empty and dry 
the dropper, draw up from the watch-glass the ten drops just 
expelled, and mark with a file on the side of the dropper the 
point up to which the ten-drop colamn extends. Mark also the 
point to which one drop (expelled and then sucked up again as 
before) will rise. 

Ten drops of the bouillon culture of the bacilli to be used 
are then expelled into each of several small test-tubes, and one 
of these tubes is carried to the bedside. After pricking the 
ear as if for blood examination' (see page 5), put the end of the 
medicine-dropper into the blood drop, and carefully draw back 
ihe rubber bulb (which has been previously pushed down over 
the glass part of the dropper) until the blood rises to the mark 
for one drop. Wipe from the outside of the dropper any blood 
that may adhere there and then expel the drop into one of the 
little test-tubes containing the ten drops of bouillon culture. In 
this way blood can be taken for examination from a dozen 
patients in as many minutes. 

2. Whole Blood— Dried, 

This method, though previously described and tested by 
Widal, was first put into effect in large numbers of cases by 
Wyatt Johnson, of Montreal, for the use of the Board of Health 
of Quebec, by whom specimens of dried blood sent by mail were 
examined and diagnoses returned as with diphtheria cultures. 
It was subsequently employed on a large scale by the Boards of 
Health of New York and Chicago. 

The advantages of the method are (a) the ease and quickness 
with which the blood can be obtained, (h) the convenience for 
transportation by mail, and (c) that it does not deteriorate or 
become contaminated by bacterial growth, as specimens of fluid 
blood or serum are so apt to do. Its clumping power is fully 
equal to that of the serum in most cases. 

• These advantages are very great and would surely lead to the 

^ Squeezing and milking the ear are of no harm in this procedure and 
enable us to get on with a trifling and painless puncture. 

^ Widal and Delepine think the fluid serum is slightly more powerful than 
the dried blood. Johnson admits that in one-tenth of the cases the serum is 
the more powerful. I have obtained reactions with the dried blood in only 
seven-eighths of the cases in which I got them with the fluid serum. 



THE CLUMP REACTION. 353 

immediate and universal adoption of this method were it not for 
the following serious drawbacks : 

(a) It is difficult to measure the amount of blood to be used in 
the test. This is important, because, as we shall see later, a 
positive reaction means not simply a clumping, but a clumping 
in a 1 : 10 dilution of the blood, to get which we need to know just 
how much blood we are dealing with. When we take the blood 
from a patient ourselves we can use the marked medicine drop- 
per, as above described, but when blood is received through 
the mails for examination or taken by any one who does not 
measure it in some way, we cannot accurately gauge the dilu- 
tion. 

(b) It is agreed by all who have used the method extensively 
that the clumping may occur with the blood of healthy people 
and hence confuse our inferences. Whether these " false clumps" 
are due, as Widal supposes, to masses of fibrin and debris in 
w^hich the bacilli become entangled, or whether they are formed 
in the ordinary way, there can be no doubt that they occur occa- 
sionally when dried blood is used. 

These objections have led most observers to prefer the fluid 
serum, but when we have not the apparatus necessary for col- 
lecting and preserving fluid serum, or when such apparatus 
could not be transported, the method is of great value. 

Procedure. — The blood should be dried either upon a glass 
slide or on a piece of glazed paper or card. Any absorbent 
substance is less available. Glass is easier to sterilize than 
paper. Several large drops should be placed in different parts 
of the glass or j^aper and thoroughly dried. 

If paper has been used, we cut out the dried blood drop with 
a pair of scissors, keeping close to the blood all round, and drop 
it into a test-tube containing one or two drops of water, in which 
with some sharp-pointed instrument we mix the dried blood, 
freeing it as well as possible from the paper. 

To the liquid so obtained add eight or nine drops of the 
bouillon culture of bacilli and proceed in the ordinary way. Or 
we may drop the fragment of paper holding the blood directly 
into ten drops of bouillon culture— using the bouillon itself to 
soak off the blood from the paper. 

When the blood is collected on glass, it may be dissolved by 
putting water on the glass and rubbing the dried blood in it 



354 



SPECIAL PATHOLOGY OF THE BLOOD. 



until a decided red tinge is obtained. A drop of this mixture is 
tlien diluted and mixed with the bouillon culture. If I rightly 
understand the communications of Johnson on this subject, he 
does not pay much attention to the dilution of the mixture of 
dried blood and water, before examination. This cannot be too 
strongly insisted on. It is true that it is impossible to make 
accurate dilutions in most specimens of dried blood received for 
examination, but we must at least make the attempt and try to 
err on the side of diluting too much rather than too little. 

A. The Fluid Serum — Quick Metliocl. 

The ear is pricked in the ordinary way and about twenty 
drops are forced out by strong squeezing. The blood is received 
in a small (preferably two-inch) test-tube, with the edge of which 
each drop is scraped off the ear ; or we may suck the blood into 
a capillary pipette and expel it again into a test-tube or other 
receptacle. There is no need of cleansing the skin or sterilizing 
the test tubes in this method of procedure, as the whole process 
is finished up so rapidly that there is no time for contaminating 
organisms to grow. 

The blood when collected may be at once centrifugalized, 
and the plasma used for the test, or we may wait till clotting 
occurs and use the serum. When blood is collected in test- 
tubes, it is convenient to free the edges of the clot from the tube 
all round with some sharp instrument, so that the serum may 
not be pinned down underneath the clot, as it often is. If this 
is done, a drop of serum can be had within two or three minutes, 
and is then mixed with ten drops of bouillon culture, as above 
described, and examined at once between slide and cover-glass. 

(Dried serum can be used in the same way as dried blood, 
but has no special advantages and has not been frequently em- 
ployed by any observer.) 

B. The Fluid Serum— Sloiv Method. 

This was the way originally described by Widal, or rather 
applied by him to the diagnosis of disease. 

The serum must be collected aseptically, and many have 
therefore preferred to take it from a vein of the elbow, which 
is punctured with a sterile syringe, as described on page 35. 



THE CLUMP REACTION. 



355 



Durham cleans the skin of the ear with a two-per-cent soki- 
tion of lysol, sucks blood into a sterile pipette, and blows it out 
again into a sterile test-tube to wait for clotting. 

Or, if we desire to keep and transport the fluid serum, it is 
sucked into the bulb of a modified Pasteur's pipette (sterile), 
such as is shown in Fig. 32, which is then sealed by heat at the 
points A and B. In this way the serum will keep for 
an indefinite period and can be sent across the ocean, 
as was recently done at the request of the New York 
Health Department. 

When we are ready to use the serum, one of the 
pointed ends of the sealed bulb is broken off and the 
serum expelled by gently warming the other end. 

The serum aseptically collected by one of the 
above-described methods is then added : 

1. To ten times its volume of bouillon culture of 
bacilli, i.e., eight drops to five cubic centimetres of 
culture, in a test-tube, which is then left from eight 
to twelve hours in the thermostat at 37° C. ; or 

2. The serum may be added to ten times its vol- 
f ume of pure sterile bouillon, and then a trace of the 

dry agar culture of bacilli added with a platinum 
loop and iJiorougJily mixed with the bouillon by rub- 
bing the loop against the inside of the test-tube, which 
is then kept twenty -four hours at 37° C. If the first 
30 of these ways is used, we get the effect of the serum 
on the fully grown bacilli ; in the second way— which 
usually needs fully twenty -four hours— it works on the nascent 
and immature organisms. 

Whichever method is used, we find that within from eight 
to twenty-four hours a remarkable change takes place in the 
appearance of the culture when serum from a case, e.g., of ty- 
phoid fever, is added to typhoid bacilli, nascent or full-grown. 
The uniform turbidity of the bouillon is gone and the liquid 
is either clear with an abundant flocculent sediment at the 
bottom of the tube, or is filled with coarse whitish particles 
separated from each other by clear bouillon. The latter change 
may take place the instant the serum is added to the culture, but 
usually needs from six to eight hours, and the full end reaction 
is often not completed till twenty -four hours elapse. Fraenkel 



356 



SPECIAL PATHOLOGY OF THE BLOOD. 



finds the reaction most marked in twelve to fourteen hours — less 
so in twenty -four (see Fig. 33) . 

A control tube containing the same proportions of the same 
culture and of a healthy person's serum should always be put 
into the thermostat along with the serum to be tested. Occa- 
sionally in such a control tube fine but visible whitish dust 
forms, hut such dust usually disap- 
pears later of itself, or can be dis- 
solved and the original diffuse tur- 
bidity produced by shaking the tube, 
while shaking a tube in which the 
true clump reaction has taken place 
will not break up the clumps nor 
restore the original turbidity. 

As above suggested, the micro- 
scopical examination of the "dust" 
seen in such a test, or of the precipi- 
tate formed at the bottom of the tube, 
shows it to be made up of clumps of 
bacilli similar to those seen in the fig. 33.— 4, complete reaction; 5. g, 
quick method, but generally larger. controls. 

The reaction is considerably less typical when the serum 
used is dark-colored, but the effects of shaking the tube and the 
comparison with the control usually enable us to decide. 

Some precipitate and clumping may occur in cases not 
typhoid: {a) when the bouillon has not been filtered and con- 
tains sediment, in which the bacilli may become entangled ; (b) 
when a large amount of the dry culture is added (in trying the 
slow method on nascent bacilli) and not thoroughly mixed with 
the bouillon ; (c) in case the platinum loop is not quite cooled 
before the agar culture is taken upon it ; (d) in case the culture 
is impure or the serum not aseptic. 

3. Blister Fluid. 

Biggs and Park find the fiuid obtained by blistering the most 
satisfactory. A fly-blister the size of a five-cent piece is applied, 
and in from six to eighteen hours a blister has formed. The 
serum from the blister is collected with a capillary tube, the 
ends of which are then sealed. This serum is admirably clear 
and free from blood corpuscles and answers the purpose well. 




THE CLUMP REACTION. 



357 



This method has never been extensively used by other ob- 
servers, except Puglieri. 

Advantages and Disadvantages of tJie " Quick Metliod " and of 
the " Sloiu Method.'' — In favor of the quick method are: (1) its 
quickness, (2) the small amount of blood needed, and (3) absence 
of any need for asepsis and of any danger of contamination. 

Against it are : (a) the occasional occurrence of pseudo-reac- 
tions or false clumps, which vi^ill be discussed on page 370; (h) 
that it needs a microscopic examination instead of being evident 
to the naked eye, as in the slow method;' (c) that it needs 
watching and cannot be left to "go on of itself." 

In favor of the slow method are : 

(1) That to some observers it appears more reliable and less 
apt to give pseudo-reactions. 

(2) That it can be seen with the naked eye. 

(3) That we do not need to watch it but simply to note the 
results at the end of from eight to twenty-four hours. 

Against it are its slowness, the danger of contamination, the 
need of a large quantity of blood and of a thermostat/ 

On the whole the great majority of observers prefer the quick 
method, and it has been used in three-fourths of the reported 
experiments. My own experience has been exclusively with 
the quick method. 

Breuer, Catrin, and Vanlair and Beco are the only ones who 
distinctly prefer the twenty-four-hour method in all cases. 

2. The Cultuees of Typhoid Bacilli to be Used. 

1. The stock cultures grow best on agar. 

2. Ordinary neutral peptone bouillon, free from sediment, is 
the best medium for the test culture. 

3. All observers agree that the cultures should be young — 
that is, that the transplantation to bouillon should have taken 
place not more than from twelve to twenty -four hours before the 
culture is used. Many observers find even the twenty-four-hour 
culture too old and prefer a twelve- to twenty-hours-old culture 
in all cases. 

' Greene states that with the quick method a mottling of the specimen can 
be seen with the naked eye. 

Pick states that no thermostat is needed, and that sedimentation takes 
place readily at room temperature. 



358 



SPECIAL PATHOLOGY OF THE BLOOD. 



4. The virulence and motility of the culture are very impor- 
tant. All observers agree that the more virulent the culture the 
more readily and characteristically it is clumped by typhoid 
serum. Biggs and Park noticed that one culture of peculiarly 
great virulence recently received from Pfeiffer of Berlin worked 
much better in their cases than any other of the cultures 
used. I have repeatedly noticed that cultures recently taken 
from autopsies on patients vrho had died during the acme of 
the fever were much more easily clumped than those taken in 
autopsies on patients who had succumbed late, after the tem- 
perature had been normal for some time. I have also noticed 
that virulent cultures grown for a long time in the thermostat 
with weekly transplantations gradually lost a good deal of their 
susceptibility to the clumping power of typhoid sera. 

Presumably these changes mean a loss of virulence in the 
culture, especially as they have always been accompanied by a 
diminution in the rapidity of motion in the bacilli. Cultures 
fresh from an autopsy usually show fir/'ioiis motility, the bacilli 
darting about like a swarm of insects, but after repeated trans- 
plantations and long sojourn in the thermostat a good deal of 
this motility is gradually lost. Cidtures kept at room iempern- 
ture preserve their rnotilitij for nu/.cJi loiK/er periods. 

For those who have no opportunity to test the virulence of 
organisms on animals, the motility is the best guide to virulence, 
and the rule should be: Arnortfj the available cidtures select that 
liavirnj tJ/e ninst rapid inotiJity. 

4, Certain cultures contain small clumps of bacilli hefore amj 
sennn has been added to tltem*. This is a very imi^ortant i3oint 
and has doubtless misled many. In consequence of this possi- 
bility every culture must be examined each time that a test is 
made. It is not sufiicient to examine each culture once for all, 
as cultures vary slightly from day to day and also vary in dif- 
ferent portions of the culture tube. For instance, ten drops taken 
from the middle of the bouillon may be found free from clumps, 
while if the next ten drops be taken from the surface or from the 
bottom of the liquid, they may contain clumps. 

This point has been strongly insisted on by Widal, Eenon, 
and others. 

5. It is hardlv necessary to say that the cultures used must 
have been submitted to all the regular tests for the recognition 



THE CLUMP REACTION. 



of the tj'plioid bacillus, and that the greatest care must be used 
to avoid their contamination. 

The Use of Suspensions or Emulsions of the Bacilli instead of 

Cultures. 

A few observers — particularly Durham and Griiber — have 
preferred to use a mixture of small bits of solid agar culture and 
bouillon instead of bouillon cultures. The majority of writers 
prefer cultures. 

The Use of Attenuated Cultures. 

Johnson found that with his methods of technique (dried 
blood and no definite dilution) pseudo-reactions were not uncom- 
mon with the blood of healthy people. 

He proposed to avoid this by using attenuated cultures — i.e., 
old stock agar cultures kept at room temperature and not trans- 
planted more than once a month, from which he planted his 
bouillon cultures. This gives a bacillus of reduced virulence 
and slow, gliding motion, which is clumped far less readily than 
the virulent varieties. Bouillon cultures of this kind from twelve 
to twenty -four hours old he found to react in fifteen minutes 
with all typhoid sera and not with other sera even after forty- 
eight hours' waiting. 

Durham, Biggs and Park, and Delepine, on the contrary, 
found such cultures unsatisfactory, in that it was not possible to 
avoid pseudo-reactions with sera of diseases not typhoid. I 
have been equally unsuccessful with this method, and believe 
with Biggs and Park that the most virulent cultures are the 
most reliable, if a proper technique is used. When dried blood 
must be used, the attenuation of cultures as advised by Johnson 
is probably a good plan. 

The Clump Reaction loitli Dead Bacilli. 

One of the most remarkable and interesting features of the 
clump reaction is the possibility of obtaining it with bacilli that 
have been killed by heat or by formol. 

Widal observed that bouillon cultures of typhoid bacilli ex- 
posed to a temperature of 57°-60'' C. for one-half to three- 
quarters of an hour lost scarcely any of their susceptibility to 
the clumping action of typhoid serum, though they are quite 



360 



SPECIAL PATHOLOGY OF THE BLOOD. 



dead. Higher temperatures (70°-120° C.) take away more 
and more of the susceptibility to clumping and also cause 
the formation of false clumps ivitJiout the addition of any serum 
ivliatever. 

Similarly one drop of ordinary formol mixed with one hun- 
dred and fifty drops of bouillon culture of Eberth's bacilli kills 
them, but apparently "embalms" them, so that their suscep- 
tibility to clumping is scarcely if at all lessened, even after the 
lapse of five months. 

The bacilli gradually sink to the bottom of the tube, but 
when shaken up distribute themselves evenly throughout the 
medium and can be used like fresh cultures for diagnostic pur- 
poses. Bordet has noted the same thing with cultures of the 
cholera-vibrio killed with chloroform. 

These facts seem at first sight to conflict with the statement 
made above, that fresh, motile, and virulent cultures are best, and 
that old ones are not reliable. But it may be, as Widal sup- 
poses, that the rapid action of heat or formol on virulent 
cultures preserves unchanged the power which prolonged 
growth in old media destroys. If this be true, it will enable 
us to dispense with our thermostat and careful nursing of 
cultures, since a single first-rate culture can be thus "em- 
balmed" and preserved for use at all times and under all cir- 
cumstances. 

Widal' s results with this method have not yet been confirmed 
by others. 

3. DHiUTION AND THE TiME LiMIT. 

/. Dilution. 

We have mentioned without explanation in various parts of 
this chapter that the blood serum or other fluids used must be 
diluted with at least ten times their volume of bouillon culture 
before any observation is made as to their action on the bacilli 
of typhoid fever. 

The reasons for this dilution and for the proportions 1 : 10 
are the following : 

It has been found, as mentioned above, that the mere forma- 
tion of clumps in bouillon cultures of Eberth's bacilli is not a 
power exclusively possessed by typhoid serum. The serum of 



THE CLUMP REACTION. 



361 



persons suffering from other diseases and even of healthy persons 
will form clumps exactly like those formed by typhoid bacilli, 
provided it is not diluted. The only known peculiarity of the 
typhoid serum is that its clumping power is greater than that of 
other diseases, and persists in spite of dilution, while the sera 
of diseases other than typhoid lose their power to clump typhoid 
bacilli when diluted ten times or more. 

11. Time Limit. 

But even this statement must be further limited. The sera 
of various other diseases, and of healthy persons, will sometimes 
clump typhoid bacilli even in a 1:10 dilution, provided ice give 
them time enough. We must therefore limit the period within 
which a serum must " come up to the scratch" and do its work, 
if it is to be considered a typhoid serum. 

Following Griiber and Durham, a time limit of one-half hour 
has been adopted by Griinbaum, Block, Haedke, Park, and 
others. 

All that these more or less arbitrary figures stand for is this : 
that hitherto no one has reported any considerable number of cases 
in which the serum of any disease or of healthy persons has clumped 
typhoid bacilli within one-half hour, when diluted 1:10 and used 
with unimpeachable technique. 

Johnson seems to be careless as to the amount of dilution, 
and Widal has not thus far admitted the necessity of a time 
limit, but the majority of careful and non-partisan observers are 
agreed that these precautions are necessary. If at any time 
cases are reported in which, despite these precautions, a clump- 
ing of typhoid bacilli has occurred with non-typhoidal sera, it 
will be necessary to raise the dilution to 1 : 15 or 1 : 20. Indeed 
there are some who think it should now be placed at one of these 
two figures. 

The clump reaction in typhoid fever is to be considered 
specific and pathognomonic only in the sense that it occurs more 
readily and in presence of greater dilution in typhoid than in 
any condition yet reported. (For details and exceptions on these 
points see page 370.) 

The serum of most cases of typhoid fever during the second 
week will clump typhoid bacilli even when diluted 1 : 40, and 
many sera preserve the power even at 1 : 100 or higher. The 
24 



362 SPECIAL PATHOLOGY OF THE BLOOD. 



following table from Biggs and Park illustrates these points 
well : 



1 Case. II 


History, symptoms, and 
diagnosis at time of taking 
blood specimens. 


Corrected 
diagnosis on 
completion 

of illness. 


Reaction of bacilli 
in broth cultures to 
serum in different 
dilutions. 


Reaction. 


Amount 

of 
serum. 


Amount 

broth 
culture. 


1 


Adult; sick four weeks, con- 
tinuous high fever; pleurisy ; 

tuberculosis " with possi- 
bility of typhoid. 


Tuberculosis. 


1 


1 


Not appreciable. 


2 


Boy; sick two weeks; con- 
tinued moderate fever, abat- 
ing when test was made; 
prostration, constipation; no 
typhoid symptoms except 
fever and prostration; 
"atypical typhoid fever." 


Uncertain. 


1 


1 


Not appreciable. 


3 


Adult; symptoms of acute 
articular rheumatism only; 
"acute articular rheuma- 
tism." 


Acute rheu- 
matism. 


I 


1 

4 
9 


Delayed moderate. 
Delayed very slight. 
Not appreciable. 


4 


Adult; just convalescent after 
sickness giving character- 
istic symptoms and physical 
signs of pneumonia; " pneu- 
monia." 


Pneumonia. 




1 

t 

19 


Immediate marked. 
Delaj^ed moderate. 
Delayed slight. 
Not appreciable. 


5 


Adult; continued high fever; 
enlarged spleen; typhoid 
bacilli obtained from spleen; 
"typhoid fever." 


Typhoid 
fever. 




1 
4 
9 


Immediate. 
Delayed incomplete. 
Delayed very slight. 


6 


Adult ; relapse after four 
weeks of continuous fever 
with typhoid symptoms; 
"relapse after typhoid fever" 


Typhoid 
fever. 


1 

10 
50 
100 
200 


Marked immediate. 
Marked immediate. 
Marked immediate. 
Delayed moderate. 
Delayed slight. 


7 


Adult; seven days continued 
high fever; typhoid symp- 
toms; two days later an 
atypical rash ; "typhoid 
fever." 


Typhoid 
fever. 




1 
9 
49 
99 
199 


Marked immediate. 
Marked immediate. 
Marked immediate. 
Delayed but marked. 
Delayed moderate. 



The Microscopic Examination. 

An artificial light is preferable. The use of hanging-drop 
preparations is unnecessary, as a simple slide and cover-glass is 
satisfactor3\ A hanging-drop cell may be extemporized by 
cementing with marine glue a small brass curtain ring to a slide, 
and inverting the cover-glass within it, as advised by Stokes. 

Sero-Diagnosis of Typhoid. 

In Table XL VI. I have collected 1,268 cases of sui)posed 
typhoid fever in which the clump reaction was tested as above 
described either with the fluid or dried blood. Of these 1,268 



THE CLUMP REACTION. 363 




364 



SPECIAL PATHOLOGY OF THE BLOOD. 



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THE CLUMP REACTION. 



365 



cases, 952 sJioived a clump reaction and turned out typJioid, 227 
shoived no clump and turned out not typhoid. That is, in 1,179, or 
93 per cen t, of the cases of suspected typhoid, the sero-diagnosis was 
confirmed by the course of the case. 

Again, out of 1,224 persons who did not have typhoid (190 
healthy and 1,034 suffering from various diseases) only 31, or 
about 2^ per cent, showed any clumping. 

How far these may be selected cases, and how true an account 
of the matter they give, we cannot of course be sure. Biggs and 
Park, in 77 hospital cases in which they were able to make re- 
peated examinations, never found the reaction wholly absent, 
although it was only slight in 9. In my own series of 77 
hospital and private cases, there were but three in which 
the reaction was absent, and of these 3, 2 were not tested 
till convalescence, and the third was tested only once, on the 
fifth day of illness, death ensuing before another test could 
be made. 

There seems to be no doubt of the fact that the serum reac- 
tion is present in some part of the course of ninety per cent of all 
cases of typhoid fever, and absent in ninety per cent or more of 
all other conditions. But it is also true that it is absent in some 
part of the course of many cases of typhoid — usually in the 
earliest or latest days of the fever — and this fact makes it neces- 
sary to retest every case in which a negative result has been 
found, and even in rare cases to make a considerable number of 
tests before a positive result is obtained. 

In 7 of my 77 cases the reaction was absent with the first test 
but present later on. This leads us to ask : Hoio early does the 
reaction appear ? 

Few of the many observers who have written on this point 
have discussed how the beginning of the disease is settled and 
what they mean, e.g., by the "fifth day of the disease." It 
might be dated from the first day of malaise and indisposition, 
from the nose-bleed or the beginning of headache, or from the 
time of going to bed. 

Allowing for such serious uncertainties as this, we find that 
while the majority of observers record the sixth to eighth day as 
the earliest on which the reaction appears, there are quite a 
number of cases mentioned in which it was seen on the fourth or 
fifth day; four articles (Fraenkel's, Pick's, Craig's, Biggs and 



366 



SPECIAL PATHOLOGY OF THE BLOOD. 



Park's) record reactions on the third day, and two (Fraenkel's, 
Sabraze and Hugon's) on the second day. 

As above mentioned, we have no way of knowing what the 
" second day" means in these cases. 

In my own observations I have called the first day in bed the 
first day of the disease (though I am aware that many patients 
are sick some time before taking to bed) , because it was the only 
date that could be definitely fixed in all cases. With this 
nomenclature I have found the reaction present on the first day 
in two cases and on the second in three cases. 

Counting from the first day on which the patient felt sick in 
any loay, the fifth day is the earliest reaction day in my series. 
In these figures we have always to remember that in no case was 
the blood tested at all previous to the day on which the positive 
test occurred, so that their meaning is: In some cases (what 
proportion of all is unknown) the serum reaction occurs at least 
as soon as the fifth day of malaise or the first day in bed, and per- 
haps sooner. 

Observations as to hoiv often we find reaction on these early 
days are confined, so far as I know, to those of Biggs and Park. 
Out of 19 cases examined between the " third and seventh day," 
12 cases, or 63 per cent, reacted positively. 

In my series, out of 20 cases examined between the first and 
seventh day of taking to bed, 17, or 85 per cent, reacted positively. 
In 2 of my cases the serum reaction was present five days before 
the appearance of rose spots or splenic enlargement. Once the 
serum reaction anticipated the diazo by two days, and in 2 cases 
it was positive when the diazo was absent throughout the disease. 

Experiments on animals show that the clump reaction ap- 
pears in the blood on the third to eighth day after inoculation 
with dead typhoid bacilli. 

How late in the disease does the reaction last ? The majority of 
observations agree that in mild cases the reaction may die out 
even before the end of the fever. On the other hand. Block has 
followed a case for one hundred and six days from the beginning 
and constantly found the clumping to occur, and Widal found it 
still present after one year in 3 out of 22 cases in which he tried 
it. These 3 subjects had had very severe cases of typhoid three, 
seven, and nine years previously. These figures indicate the 
limits. Biggs and Park found the reaction more constant in 



THE CLUMP REACTION. 



367 



the fourth week than at any other time — 76 per cent of his 
cases tested between the thirtieth and sixtieth days still showed 
the reaction, and 5 of 8 cases still reacted after three to four 
months. 

The reaction almost always persists in relapses, even to a 
second or third relapse, and occasionally it is present only in 
relapse and not in the original attack at all. Biggs and Park 
record a case in which the diagnosis was proved during the 
original attack by puncture of the spleen, which showed a pure 
culture of Eberth's bacilli, yet no serum reaction was present 
until the second day of the relapse. I have observed two similar 
cases. In one of Elsberg's cases the total duration of the clump- 
ing power in the blood was only eight days ; in another only 
twelve days. 

The continuance of the reaction after the fall of the tempera- 
ture is no indication (as some have supposed) that relapse is 
coming, for in many such cases no relapse follows. 

The Intensity of the Reaction. 

Widal and others have studied the intensity of the reaction 
at different periods of the disease, judging by the amount of 
dilution which could be practised without destroying the power 
of a given serum. 

Examples of this have already been given in the table on page 
363. The majority of typhoids in the second and third week 
yield serum which will clump Eberth's bacilli when diluted 1 : 40 
and many cases will do so even at 1 : 100. Strangely enough, 
some typhoid sera clump better when diluted 1 : 16 or more 
than when undiluted. This has been repeatedly noted by 
Griinbaum. 

Widal and Sicard record clumping with a dilution of 1 : 12,000 
and 1:1,800 and consider that in the active stages of the dis- 
ease a dilution of 1 : 60 or 1 : 80 does not usually present the re- 
action, while in convalescence the power of the serum falls off 
gradually and is not always present even at 1 : 10. 

Biggs and Park find one-half their typhoid cases furnish 
serum with the power to clump in 1 : 40 dilution by the end of 
the first week, and have occasionally noted the reaction even 
with a dilution of 1 : 200. 

Jemma found the reaction most intense at the acme of the 



368 



SPECIAL PATHOLOGY OF THE BLOOD. 



fever and greater during tlie evening exacerbation of fever than 
in the morning. 

Effects of the Sera of Other Diseases. 

Negative results are reported in the following list of diseases 
experimented on as controls : Pneumonia, typhus, Malta fever, 
tuberculosis in its various forms, including miliary tuberculo- 
sis, tubercular meningitis, pneumococcus meningitis (purulent) 
and epidemic cerebro-spinal meningitis, diphtheria, influenza, 
ulcerative endocarditis, erysipelas, puerperal septicaemia, gonor- 
rhoeal septicaemia, measles and scarlet fever, tonsilitis, acute 
articular rheumatism, malaria, leprosy, syphilis, bronchitis, 
pleurisy with effusion, acute and chronic nephritis, mumps, oti- 
iis media, catarrhal jaundice, sciatica, acromegalia, hysterical 
vomiting. Graves' disease, gangrene of the lung, appendicitis, 
abscess and cirrhosis of the liver, acute febrile gastro-enteritis 
("embarras gastrique"), cancer of the various organs, alveolar 
abscess with fever, osteomyelitis, bubo with fever, arthritis de- 
formans, chronic laryngitis, intestinal obstruction, general peri- 
tonitis, leukaemia, Hodgkin's disease, pernicious anaemia, diar- 
xhoea, chronic gastritis, gallstone colic with fever, dysentery, 
acute mania, stuporous melancholia, synovitis, neurasthenia, 
v^aricose veins, orchitis, suppurative thyroiditis, perinephritis, 
cystitis, pericarditis, empyema, brain abscess, valvular heart 
disease, diabetes, gas poisoning, alcoholism, and eclampsia. 

The important diseases of this list, such as pneumonia, 
tuberculosis, meningitis, and typhus, have been tried many 
times. Biggs and Park got a positive result in one case said 
to be typhus. There is a chance of mistaken diagnosis here. 

Positive Besults of the Sera of Other Diseases luitJi TypJwid 

Bacilli. 

Many of the supposed contradictions of the law, that the 
typhoid bacilli are cliimijed within one-half hour only by typhoid 
serum luhen a dilution of one part of serum to ten or more of culture 
is used, are due to faulty technique. Such are probably the cases 
reported by Ferrand and Theoari (septicaemia), Yillies and 
Eattle (malaria), Gehrmann and Wynkoop (pneumonia, bron- 
chitis, pleurisy), and Stern (otitis media). 



THE CLUMP REACTION. 



369 



On the other hand there are a few cases reported by careful 
observers in which a genuine clumping of typhoid bacilli has 
been caused by the sera of other diseases, viz. : Pernicious 
malaria, comatose, one case (Block) ; diabetic coma, one case 
(Block) ; jaundice, one case (Catrin) ; tubercular meningitis, one 
case (Jez). 

A case of malaria, reported by Catrin, with positive reaction 
of the serum on typhoid bacilli, was in a subject who had had 
typhoid five years before. In view of Widal's and Fraenkel's 
results, this cannot be counted an exception to the general law. 
The same is true of Griinbaum's much-quoted cases, which he 
reported not as exceptions but to emphasize the necessity of 
proper dilution. Using a proportion of 1 : 1 instead of 1 : 10, he 
got clumping of typhoid bacilli with the sera of jaundice (two 
cases), meningitis and bronchitis (one case each). 

The cases reported by Johnson, Braunan, Thomas, Keed, 
and other observers, in which the dried blood of healthy per- 
sons and persons with various diseases other than typhoid has 
clumped typhoid bacilli, are probably owing to the uncertain- 
ties connected with that method of procedure. 

In most cases in which the fluid serum was also tried it gave 
no reaction. 

The discovery that the bacillus of psittacosis and the " bacillus 
enteritidis" of Gartner are somewhat sensitive to the action of 
typhoid serum (see page 372) has led to the fear that infec- 
tions due to those bacilli might be mistaken for typhoid, but 
this is wholly an assumption, as in the few cases of these infec- 
tions which have been studied the serum has not affected typhoid 
bacilli. 

Further, it is only by a concentrated artificial typhoid serum 
that the bacillus of Gartner is clumped, and the clumping of the 
psittacosis bacillus is quite different from that of the typhoid 
bacillus, the clumps of the former being very small and few; 
with the twenty-four-hour method no precipitate forms. 

Summary of Negative Results. 

Out of over one thousand cases of various diseases not 
typhoid, but four have been proved to clump typhoid bacilli 
with proper technique. It is quite possible that further im- 



370 



SPECIAL PATHOLOGY OF THE BLOOD. 



provements in technique ma}^ enable us to prevent even this very 
small error. 

Effects of Typhoid Serum on Other Bacilli. 
(a) On the Bacillus Goli Communis. 

Any blood serum mixed 1 : 10 with a bouillon culture of colon 
bacilli may cause the formation of small clumps without consid- 
erable loss of motility. The effect of typhoid serum does not 
differ from that of other sera, and the clumps which it forms are 
much smaller and looser than those seen in the typical typhoid 
clump reaction. Different cultures of colon bacilli differ a good 
deal in their susceptibility to typhoid serum, and Vanlair and 
Beco consider that no difference can be made out in certain cases 
between its effects on typhoid bacilli or on colon bacilli. The 
majority of observers, however, find a decided difference, espe- 
cially with the twenty-four-hour method. Undiluted typhoid 
serum acts more strongly on colon than on typhoid bacilli, ac- 
cording to Griinbaum. 

Biggs and Park found that " a number of varieties of motile 
bacilli other than typhoid bacilli are clumped by the serum of 
persons suffering from typhoid fever, even when the serum is 
used in quite high dilutions." 

Eodet noted that only a very slight effect is produced by ty- 
phoid serum on colon bacilli until a dilution of one part of serum 
to two of culture is reached. 

Fraenkel tested a large number of colon cultures without 
getting any decided effect from the addition of typhoid serum. 

Courmont found that some cultures of the colon bacillus are 
clumped by typhoid serum. 

Widal saw no difference between the effect of typhoid serum 
and that of other sera on colon bacilli, but Vedel thinks that 
young cultures are better clumped by typhoid serum than by 
other sera. 

Johnson, who studied a large number of cases, says : " A 
complete colon reaction we have found to be exceptional in or- 
dinarj^ typhoid, and its presence would indicate a condition of 
coli intoxication," which may be held to sum up the discussion 
up to the present time. 



THE CLUMP REACTION. 371 

(6) On the Bacillus Enteriticlis {Gartner). 

Griiber and Durham, using powerful artificial sera from 
animals immunized against Eberth's bacillus, were able to obtain 
a clumping of Gartner's organisms. No experiments with hu- 
man serum are recorded. 

(c) On the Bacillus of Psittacosis. 

Psittacosis is a disease affecting parrots and occasionally 
transferred by them to human beings. A bacillus has been 
found by Nocard in the marrow of the parrot's wing-bones which 
is considered the cause. Typhoid serum has an effect on 
bouillon cultures of this bacillus, which is to be distinguished 
quantitatively from the clumping of typhoid bacilli by typhoid 
serum; the heaps of psittacosis bacilli are much fewer and 
smaller, and in the twenty-four-hour method the turbidity of the 
cultures does not disappear. 

(d) The Klehs-Loejffier Bacillus and Pas Cocci. 

Courmont finds that typhoid serum clumps Klebs-Loefiier 
bacilli and staphylococci, but is without effect on the strepto- 
coccus and the bacillus pyocyaneus. 

Summary of Clinical Evidence on the Sero-Diagnosis of 
Typhoid Fever. 

The blood of over ninety per cent of all cases of typhoid 
shows a clumping power in some part of their course, but in at 
least half the cases this does not appear until the second week 
of the disease, while in a small number of cases it first appears 
in relapse. The clumping power may disappear before the 
defervescence and may be present only eight days in all; as a 
rule it persists from the sixth or eighth day until convalescence 
is established. 

In diseases other than typhoid a clump reaction is very 
rarely to be obtained, provided a dilution of at least 1 : 10 is 
used with a time limit of one-haK hour. There is no one dis- 
ease in which clumping is especially apt to occur. 

Clinically the reaction is of considerable value, especially 
when the diagnosis is in doubt after the first week of the dis- 
ease. 



372 



SPECIAL PATHOLOGY OF THE BLOOD. 



Seed-Diagnosis of Diseases Other than Typhoid. 
1. Cholera. 

Griiber and Durham first showed that human cholera serum 
would clump cholera vibrios, following the researches of Pfeiffer 
in vivo by demonstrating a similar reaction in vitro. 

Achard and Bensaude have applied this to the actual diag- 
nosis of cholera in man with considerable success. 

2. Pyocyanetis Infections. 

The bacillus pyocyaneus has been shown to be in all proba- 
bility the cause of certain cases of dysentery, broncho-pneu- 
monia, otitis media, nephritis, pericarditis, cystitis, and of a 
hemorrhagic septicaemia with enteritis in the new-born. 

Eoger and Charin found in 1889 that the bacillus pyocyaneus 
is serum of animals immunized against this bacillus. Durham 
repeated these observations in 1895 and confirmed them. 

Here we have the clinical infection and laboratory clump- 
reaction experiments, but so far as I am aware no one has yet 
brought the two together or tried the serum of patients with 
pyocyaneus infections on cultures of the bacillus. 

3. Diphtheria. 

Widal reports no success in attempts at the sero-diagnosis 
of diphtheria, and Fraenkel has not been more successful. 
Nicolas and Charrin found that, although no true serum reaction 
could be obtained in diphtheria previous to antitoxin treatment, 
the injection of antitoxin produces in the patient's serum a de- 
cided clumping power over the Klebs-Loeffler bacilli within 
twenty-four hours of the time of injection. This is especially 
marked in the twenty-four-hour method, using the nascent bacilli, 
as described on page 356. The serum retains its clumping power 
for about two weeks after the injection of antitoxin, and then 
gradually loses it. Outside the body the diphtheria antitoxin 
easily clumps Klebs-Loeffler bacilli. 

4. Pneumococcus Infections. 
Washburn in 1895 noticed that pneumococci, when mixed with 
artificial anti pneumococcus serum and left twenty-four hours at 
37°C, were clumped in masses at the bottom of the tube, leaving 



THE CLUMP REACTION. 



373 



the upper portions of the liquid clear. In other words he got a 
tj^pical twenty-four-hour clump reaction, using a powerful ar- 
tificial serum. The same fact had previously been observed by 
Metchnikoff in 1891 and by Issaef in 1892, and has been recently 
confirmed by Mosny. 

Widal has been entirely unsuccessful in finding any clumping 
with the serum of pneumonia patients, and Block finds the 
clumping of pneumococci very slow and unsatisfactory. 

5. Colon-Bacillus Infections. 

In view of the frequent association of this bacillus with dis- 
ease, especially with the cystitis of oung girls, it is important 
that the possibility of a sero-diagnosis of colon-bacillus infec- 
tions should be studied, but as yet very little has been done in 
this direction. 

Griiber and Durham showed that serum from animals arti- 
ficially immunized against the colon bacillus would clump that 
bacillus strongly, but Widal' s experiments with supposed cases 
of colon-bacillus infection did not show any decided reaction, 
nor did the serum of typhoids which showed post mortem a 
secondary colon-bacillus infection react during life on cultures 
of this bacillus. 

On the other hand Vedel reports a case with the clinical 
aspect of typhoid yet with no serum reaction, in which there 
was a marked reaction with the colon bacillus. In this case 
defervescence occurred on the tenth day, and Vedel is inclined 
to believe that some cases hitherto considered as mild or abor- 
tive typhoid can be shown by the serum reaction on the colon 
bacillus to be due to that organism. 

Johnson has been " struck by the large proportion of positive 
colon reactions obtained in cases having ' step-ladder ' tempera- 
ture and other symptoms strongly resembling typhoid but with- 
out the typhoid-serum reaction." He thinks that "under these 
circumstances the colon reaction may have a real diagnostic im- 
portance, and indicates that the colon infection, whether occur- 
ring alone or as a secondary complication of typhoid, may be 
playing an important part in the production of the patient's 
condition. The whole question of associated colon infection 
deserves further study." 



374 



SPECIAL PATHOLOGY OF THE BLOOD. 



6. Malta Fever. 

Wright and Smith tested the serum of 15 cases of Malta 
fever with the micrococcus melitensis of Bruce, and found a strong 
clump reaction to occur (1 :50 in most cases). On the typhoid 
bacillus the serum of these cases had no action. Sixteen cases 
of typhoid showed no reaction with Bruce's organism. The 
evidence in favor of this organism as the cause of Malta fever is 
strengthened by these facts. 

7. Peripneumonia of Catile and Hog Cholera. 

Arloing finds that the serum and other body fluids of cattle 
suffering from peripneumonia have a marked clumping power on 
the pneumobacillus bo vis. 

Dawson has had similar positive results working with the 
bacillus of hog cholera. Hog-cholera serum had no effect on 
the typhoid or colon bacillus. 

8. Proteus Infections. 

Infections with the proteus vulgaris or proteus mirabilis 
have been considered causative in cases of mastoid abscess, 
meningitis, and Potts' disease. When found by culture at 
autopsies the question often arises whether they have wandered 
in after or at the time of death, or whether they were really con- 
cerned in the etiology of the case. The investigations of Achard 
and Lannelongue appear to give us the means of answering this 
question. They found that cultures of the two species of pro- 
teus above mentioned were markedly clumped b}^ the serum of 
animals rendered immune to them b}^ inoculations. This power 
persists after death and even in putrefaction, and if present at 
any given autopsy proves that the infection did not take place 
during the last two days of life, since it takes at least three days 
to bring the clumping power into the serum by artificial inocu- 
lation. 

9. Oidium Albicans. 

Eoger showed that the oidium was well clumped by the 
serum of animals immunized against it, and these observations 
have been confirmed by Charrin and Ostrowsky. No experi- 
ments with human thrush have as yet been reported. 



THE CLUMP REACTION. 



375 



10. Miscellaneous Beporfs on Other Infections. 

(a) Griinbaum {Lancet, Februar}^ 13th, 1897) states that a 
" non-motile diplococcus" from a case of scarlet fever was clumped 
by the serum of another case of scarlet fever. 

{b) Delepine {Medical Chronicle, October, 1896) refers to suc- 
cessful experiments with the tetanus bacilli — its antitoxin hav- 
ing a decided clumping action upon it. 

{c) Durham {Lancet, loc. cit. ) speaks of the present antistrep- 
tococcus serum (Marmorek's) as having strong clumping power 
on streptococci. 

{d) Gilbert and Fournier (Compt. rend, de la soc. de biol., 
December 25th, 1896) mention two cases of human psittacosis 
whose serum clumped well the bacilli obtained from another 
human case as well as those taken from parrots. Clumping was 
present on the fourth and fifteenth days respectively. 

The Natuee of the Clumping Pkocess and of the Clumping 

Substance. 

1. The question as to whether or not the clumping reaction 
in typhoid is " specific'' has been much debated. Most observers 
are now agreed that whatever right it has to the term " specific'' 
rests on the fact that typhoid serum will clump in greater dilu- 
tion than that of any other known disease. It is a quantitative, 
not a qualitative affair. 

2. Discussion has also raged round the question whether the 
clump reaction expresses immunity, or whether, as Widal has 
steadily maintained, it is a reaction of infection. 

Certainly we must modify our usual ideas of immunity if it 
is expressed by a reaction which can appear as soon as the 
symptoms do, disappears frequently during or before conva- 
lescence, and is present just before relapse. Further, Achard 
found that the serum which had lost its clumping power on the 
tenth day after defervescence conferred as great an immunity on 
animals as the serum of the same patient taken during the heiglit 
of the disease and of the clumping power of the serum. Bacilli 
when not clumped are not destroyed and will grow freely if re- 
planted; serum will clump after being heated to 59° C. ; so that 



376 



SPECIAL PATHOLOGY OF THE BLOOD. 



its power is evidently not bactericidai, and its action on dead 
bacilli would be hard to explain as — bactericidal! 

These considerations seem to the majority of observers con- 
clusive evidence against the propriety of the use of the word 
immunity. On the other hand, it is strange that a reaction of 
infection should be intense in mild cases and absent in very 
severe ones, as has occurred. 

The clumping powers of the serum are evidently distinct both 
from its natural and non-specific bactericidal power (Buchner's 
" alexins") and from the specific immunity against a given dis- 
ease which may be artificially conferred, as by diphtheria anti- 
t-oxin. That various organisms other than typhoid are clumped 
and attenuated by their appropriate antitoxins (diphtheria, etc., 
see above), does not prove that the preventive and clumping 
powers are identical in typhoid, but only shows that in those 
particular preventive sera the power to clump their appropriate 
bacilli is present as well, perhaps owing to peculiarities in 
horse 's-blood serum. 

3. The loss of motility in connection with the clumping is 
probably a by-action of the serum, perhaps an expression of 
its natural bactericidal power, as various other sera will check 
the motility of typhoid bacilli, and dead, motionless bacilli 
clump as well as those that are motile (see page 360). 

Nature of the Clumping JSuhstance. 

Widal and Sicard have shown that in typhoid serum or other 
actively clumping fluids (see page 351) the clumping power 
resides in the globulin and fibrinogen, and not at all in the serum 
albumin. This globulin of typhoid blood is identical chemi- 
cally with the globulin of normal blood (Devoto). 

In milk it is the casein (lacto-globulin) that possesses the 
clumping power. 

Filtration through porcelain destroys or greatly attenuates 
the clumping power. It seems not to pass the placenta in 
human infections, as the observations of Etienne, Apert, and 
Charrin have failed to find it in the fluid of infants born of 
typhoid mothers. On the other hand, Widal - and Sicard did 
find it in the litter of an immunized rabbit. It will pass through 
parchment. 



THE CLUMP REACTION. 



377 



A temperature of 66° C. does not destroy- it, and even after 
ten minutes at 75°C. it is not wholly gone; 80^C. wholly de- 
stro3^s it. 

Achard and Bensaude made a set of careful studies to ascertain 
whether the leucocj^tes were responsible for the clumping action 
of the serum through their secretory power. (The fact that 
blister fluid free from leucocytes clumps well, excludes any de- 
pendence of the reaction on their actual presence.) They sepa- 
rated and kept alive the leucocytes of typhoid blood whose se- 
rum clumped strongly. These were washed with artificial serum 
until the filtrate gave no clump reaction; a liquid was then 
squeezed out of them by strong pressure. This liquid gave no 
clump reaction, yet the leucocytes were still alive enough to 
take up carmine granules. 

Two more facts relative to the clumping power must be added, 
though they confuse rather than clarify our ideas. 

1. The serum of normal horses has strong clumping power 
on typhoid, cholera tetanus, and colon bacilli. 

2. Chrysoidin has been shown by Blachstein to possess the 
power to clump the vibrio of Asiatic cholera, though it has no 
effect on allied vibrios nor on other bacilli. Substances chemi- 
cally very close to chrysoidin are inert in relation to the cholera 
vibrio. 

Sero-Peognosis. 

It is agreed by all observers that in a very general way severe 
cases have more marked reactions than mild ones, but beyond 
this, in the opinion of the best judges, we cannot yet go. 

Widal, Fraenkel, Biggs and Park, and Johnson have at- 
tempted no sero-prognosis, and my own observations are entirely 
in accord with this. The reaction may be strong in mild cases 
and feeble or absent in fatal ones. 

Certain writers, however, especially Breuer, Courmont, 
Catrin, and UUmann and Wohnert, have thought the reaction of 
prognostic value, an intense and early reaction seeming to them 
of evil omen. Further evidence on this point is much needed. 

LFor bibliography, see page 428.] 
25 



APPENDIX. 



Neusser's Perinuclear Basophilic Granules. 

Using the following modification of Eliiiicli's tricolor mix- 
ture, Neusser' believes that he can bring out certain character- 
istics in the leucocytes of value in diagnosis and prognosis. 



( Acid fuchsin 50 c. c. 

Saturated aqueous solution of < Orange G 70 " 

( Methyl green 80 " 

Distilled water 150 " 

Absolute alcohol 80 " 

Glycerin 20 " 



Cover slips stained with this mixture show in certain dis- 
eases (e.g., gout, leukaemia) a grouping of dark blue-stained 
^granules around the nuclei of the mononuclear leucocytes and 
over and around the nuclei of polymorphonuclear leucocytes. 
These granules appear to take up only the basic part of the 
iri-color mixture. 

For Neusser's conclusions regarding the meaning of these 
granules, the reader is referred to pages 222 and 276. 



1 Wien. klin. Woch., 1894, No. 39. 



BIBLIOGRAPHY. 



It has seemed to me best to give a list of the books and 
articles which I have found most useful, classing those found 
less valuable with the general bibliography. 

Text-Books. 

1. Hayem : " Du Sang," Paris, 1889, Svo, 1035 pages (French). This 
valuable book is the largest that I know of on the subject, and contains 
a mine of information on the morphology of the blood in health and 
disease, mostly from the author's own experience, literature being but 
little referred to. It contains a comparative anatomy of the blood 
and a long account of blood development. Unfortunately, it is domi- 
nated throughout by a theory of blood formation which has never 
gained acceptance by any other authority. It is very full on the sub- 
ject of fibrin formation and of chlorosis. The illustrations are excel- 
lent. 

2. V. Limbeck : " Grundriss ein. klin. Pathologic des Blutes," Jena, 
1896, Svo, 383 pages (Fischer). The second edition of this book, which 
appeared in February, 1896, is more than twice the size of the first edi- 
tion (1892)— a fact illustrating the rapidity of the subject's growth. It 
is on the whole the best general text-book known to me, being equally 
full on all parts of the subject, including, for example, technique 
(which Grawitz omits) and of the chemistry the blood, which is at 
present the author's special interest and on which Hayem is meagre. 
The illustrations are poor and the type is trying to the eyes. The 
writer shows little personal experience with the morphology and micro- 
chemistry of the blood, and this is the weakest side of the book. A 
large part of the book is concerned Avith the physiology of the blood. 

3. Grawitz: " Klinische Pathologic des Blutes," Berlin, 1895, Svo, 
333 pages (Enslin). Issued in April, 1896. This book is the latest 
known to me. It is largely devoted to the matter indicated by the 
title and contains no account of blood technique, and only thirty pages 
on the normal anatomy and physiology of the blood, while two 
hundred and seventy concern the blood in disease. The arrangement 
of the book is very clear and helpful. The author's main interests are 
in the estimation of the dried residue of the blood in various diseased 
conditions and in the bacteriology of the blood, so that the book is 
specially full on these topics. The illustrations are poor. Type and 
paper are excellent. 



380 



BIBLIOGRAPHY. 



4. Schmaltz: " Pathologie des Blutes und die Blutkrauklieiten," 
Leipzig, 1896, 16mo, 268 pages (Naumann). A much smaller book than 
either of the others and including the symptoms, pathology, and 
treatment of blood diseases, as well as a pathology of the blood itself. 
Specific gravity of the blood is a point of special interest with the 
author. There are no illustrations. The book is excellent as far as it 
goes, well arranged, and clear. 

These are the best text-books known to me on the whole 
subject. None of them have been translated. 

Text-Book Articles on Blood Diseases. 

1. Osier, in the "American Text-book of the Theory and Practice 
of Medicine," vol. ii. (Philadelphia, 1894, Saunders), writes a fifty-page 
article on " Diseases of the Blood," which is the standard work on the 
subject in English. It covers, of course, only the blood diseases proper 
without much account of the blood in other conditions. 

2. Stengel's article in vol. vii. of the "Twentieth Century Practice 
of Medicine " is excellent. 

3. The article "The Blood in Infancy," in Rotch's Paediatrics, covers 
this branch of the subject very thoroughly and is up to date (1895). 

These are the best articles in English that I know of. 

4. The article on " La Pathologie du Sang," by Gilbert, in the five- 
volume " Traite de Medecine" edited by Charcot, Bouchard, and 
Brissaud, Paris, 1892 (Masson), is inferior to those last mentioned and 
is mostly an echo of Hayem's work above referred to. Theories long 
exploded {e.g., that eosinophiles are pathognomonic of leukaemia) 
receive the author's sanction. The article is one hundred large octavo 
pages long and is intended to cover the whole subject. 

5. Griffith's eighty-page article in Keating's ' ' Cyclopaedia of the 
Diseases of Children," vol. iii., p. 755 (Philadelphia, 1890, Lippincott), 
is now a good deal out of date. 

6. The articles on blood diseases in the latest editions of the text- 
books of Osier, Strtimpell, Da Costa, Flint, and Pagg, contain relatively 
little about the blood itself. 

Treatises on Special Portions of the Subject. 

1. Reinert's "Die Zahlung der Blutk5rperchen " Leipzig, 1891 
(V ogel), 246 pages, is an admirable account of the avoidable and un- 
avoidable errors in blood examination, and the best methods of re- 
ducing error to a minimum. A number of careful examinations of the 
blood in health and in various diseases are also given ; and an outline 
of the scope of blood diagnosis closes the book. 

2. Rieder's " Beitrage zur Kenntniss der Leukocj^tosis," Leipzig, 
1892 (Vogel), 220 pages, is an admirable work in all respects, although 



BIBLIOGRAPHY. 



381 



now considerably out of date. It shows, as veiy few of the foregoing 
treatises do, a practical acquaintance, on the author's i^art, with the 
details of blood morphology and microchemistry. A very large num- 
ber of blood counts in many diseases is recorded. 

3. Lowitt's "Studien zur Physiol, und Pathol, des Blutes u. der 
Lymphe " (Jena, 1893 [Fischer], 8vo, 138 pages) is mostly concerned 
with experiments on animals and intended to throw light on the 
theory of leucocytosis. The conclusions of the book have not been 
generally adopted, though its facts have been mostly verified, 

4. Thayer and Hewetson's book, on the " Malarial Fevers of Balti- 
more," leaves nothing more to be desired in that direction. It is two 
hundred and fifteen pages long, published by the Johns Hopkins press 
of Baltimore in 1895. It contains a summary of the literature of the 
subject, an analysis of six hundred and sixteen new cases, and some 
admirable colored plates. It is a model of its kind in every respect, 
and an ideal for others to aim for. 

5. Ehrlich's " Farbenanaly tische TJntersuchungen " (Berlin, 1891 
[Hirschwald], 137 pages) contains nine short essays by Ehrlich and 
three by his pupils. Considering the reputation of the writer they 
are at the present day rather disappointing reading and contain little 
that is not better expressed elsewhere. 

6. Under a somewhat different heading come the sections on the 
examination of the blood in v. Jaksch's "Clinical Diagnosis" (English 
translation, London, 1893, Griff en & Co.), a seventy-five-page article 
containing many inaccuracies; and Lenharz : ''Microscopic und 
Chemie am Krankenbett " (Berlin, 1896, Springer), a fifty-page article. 

Magazine Articles of Special Value. 

1. On Concentration and Dilution of the Blood — Oliver : Lancet, 
June 37, 1896. 

3. On the i^^ature of Leucocytes — Gulland: Journal of Physiology, 
May 30, 1896, London. 

3. On Leucocytosis — Krebs : Inaug. Dissert., Berlin, 1893. Sadler: 
Forschr. d. Med., Supplement-Heft, 1893. Also Klein, in Volkmann's 
Sammlung klinischer Vortrage, December, 1893. and of course Rieder, 
above referred to. 

4. On Ansemia — Dunin : Volkmann's Sammlung. klin Vortrage, 
1896, No. 135. 

5. Parasitic Anaemia — Schaumann : Zur Kenntniss der sog. Both- 
riocephalus Anamie, Berlin, 1893, 314 pages ; and Askanazy : Zeitschr. 
f. khn. Med., 1895, p. 493. 

6. Leukaemia — Fraenkel : Deutsche med. Wochenschrift, 1895, 
p. 639. 

7. Pernicious Anaemia — Discussion by Birch-Hirschfeld, Ehrlich, 
Troje, and others, at the XL Congress f. inner. Med. (Leipzig, 1893). 

8. Pneumonia— Billings : Bulletin of the Johns Hopkins Hospital, 
November, 1894. Diphtheria— Billings: New York Medical Record, April 



382 



BIBLIOGRAPHY. 



25, 1896. Typhoid— Thayer : Johns Hopkins Hospital Reports, vol. iv., 
No. 1. Exanthemata— Felsenthal : Arch. f. Kinderheilk., 1892, p. 78. 
Zappert : Zeitschr. f. klin. Med., 1893, No. 23. Small-pox— Pick : Arch, 
f. Dermatol, und Syph., 1893, p. 63. Sepsis— Roscher : Inaug. Dissert., 
Berlin, 1894. Cholera — Biernacki : Deutsche med. Wochenschr., 1895, 
No. 48. 

9. Syphilis— (a) Reiss : Arch. f. Dermat. und Syph., 1895, Hf. 1 and 
2. (&) Justus : Virchow's Arch., 1895. 

10. Tuberculosis — (a) Dane : Boston Medical and Surgical Journal, 
May 28, 1896. (b) Stein und Erbmann : Deutsche med. Wochenschr., 
1896, No. 56, p. 323. (c) Grawitz : Deutsche med. Wochenschr., 1893, 
No. 51. 

11. Malignant Disease — {a) Sadler : Loc. cit. (b) Reinbach : Lan- 
genbeck's Archiv, 1893, No. 46. (c) Strauer : Dissert., Greifswald, 1893. 

12. Bacteriology — Sittmann : Deutsches Arch. f. klin. Med., vol. 53. 

13. Diseases of the Stomach (especially Cancer) — Schneyer : Zeit- 
schrift f. klin. Med., 1895, p. 475. Osterspey : Inaug. Diss., Berlin, 1892. 

14. Eosinophiles— Zappert : Zeitschr. f. klin. Med., 1893, vol. 23. 

Technique. 

Biernacki : Zeitschr. f. physiol. Chemie, Bd. 19, S. 179. 
Bleibtreu, M. u. L. : Eine Methode zur Bestimmung der kCrper- 
lichen Elemente im Blute. Pfliig. Arch., Bd. 51, 1892, S. 151. 
Bizzozero : Handbuch der klin. Mikroskopie, Erlangen, 1883. 
Cohnstein u. Zuntz : Pfluger's Arch., Bd. 42, 1888. 
V. Fleischl : Wien. med. Jahrb., 1885, S. 425. 

Gartner : Ueber eine Verbesserung des Hamatokrit. Berl. klin. 
Wochenschr., 1892, S. 890. 

Gartner u. Romer : Wien. klin. Wochenschr., 1892, No. 2. 

Grawitz, E. : Klinisch-experimentelle Blutuntersuchungen. Zeit- 
schr. f. khn. Med., Bd. 21, 1893, H. 5, 6. 

Hammerschlag : Wien. klin. Wochenschr., 1890, S. 1018. 

Hamburger : Die physiol. Kochsalzlosung und die Volumbestim- 
mung der kdrperl. Elemente im Blute. Centralbl. f. Physiol., 1893, 
und ibidem, 1894, S. 656. 

Hedin : Ein neuer Apparat zur Unters. des Blutes. Skand. Arch, 
f. Physiol., 1890. 

Heidenhain : Versuche und Fragen zur Lehre von der Lymphbil- 
dung. Pfltiger's Arch., Bd. 49, 1891. 

Hoppe-Seyler : Zeitschr. f. phys. Chemie, Bd. 16, S. 505. 

V. Jaksch : 1. Ueber die Zusammensetzung des Blutes gesunder 
und kranker Menschen. Zeitschr. f. klin. Med., Bd. 23, 1893. 2. 
Ueber den iV-Gehalt der roten Blutzellen des gesunden und kranken 
Menschen. Zeitschr. f. klin. Med., Bd. 24, 1894, S. 429. 

Kraus : Ueber die Alkalescenz des Blutes in Krankheiten. Zeit- 
schr. f. Heilk., Bd. 10. 

Lackschewitz : Ueber die Wasseraufnahmefahigkeit der roten Blut- 
k5rperchen. Diss., Dorpat, 1892. 



BIBLIOGRAPHY. 



383 



Landois : 1. Eulenburg's Realencyklop., 2te Aufl., Bd. vii., S. 570. 
2. Lehrbuch der Physiologie, 1893. 

Leichtenstern : Unters. tiber den ^&-Gehalt des Blutes, etc., Leip- 
cis, 1878. 

V. Limbeck : Grundriss einer klinischen Pathologic des Blutes, 
Jena, 1896. 

Lloyd Jones : Journ. of Physiol., t. viii., 1887. 

Lowit : Studien zur Physiologic und Pathologic des Blutes, etc.» 
Jena, 1892. 

L5wy : Unters. zur Alkalescenz d. Blutes. Pfltiger's Arch., Bd. 58^ 
1895, S. 462. 

Lowy-Zuntz : Ucber die Bindung der Alkalien in Scrum u. Blut- 
kCrpcrchcn. Pflug. Arch., Bd. 58, 1895, S. 511. 

Lukjanow : Grundzilge einer allgem. Pathologic d. Gefassystcms, 
Leipsic, 1894. 

Pfeiffer, Th. : Ueber die Bleibtreu'sche Methode zur Bestimmung 
des Volumcns der kOrperl. Elcmentc im Blute, etc. Centralbl. f . inn. 
Med., 1895, No. 4. 

Reinert : Die Zahlung der rothen Blutkorpcrchen, Leipsic, 1891. 

Schmaltz: Die Untersuchung d. spcz. Gew. d. menschlichen 
Blutes. D. Arch. f. klin. Med., Bd. 47, 1891. 

Schmidt, Alex. : Zur Blutlehre, Leipsic, 1892. 

Schultz-Schultzenstein : Centralbl. f. d. mediz. Wissensch., 1894, 
S. 801. 

Stein, H. : Centralbl. f. klin. Med., 1892, No. 23. 
Stintzing : Zur Blutuntersuchung. Verhandl. d. XII. Congr. f. 
inn. Med., 1893. 

Winternitz : Centralbl. f. klin. Med., 1893, S. 177 u. 1017. 

Red Corpuscles. 

Afanassiew, M. : Ueber den dritten Formbestandtheil des Blutes 
im normalen und pathol. Zustande und iiber die Beziehung desselben 
zur Regeneration des Blutes. Deutsch. Arch. f. klin. Med., xxxv., 
1884, S. 217. 

Askanazy : Zeitschr. f. klin. Med., 1895, Bd. 27, S. 492. 

Biernacki, E. : Ueber die Beziehungen des Plasmas zu den r. Bl. 
und iiber den Werth verschiedener Methoden der^ Blutkorperchen- 
volumbestimmung. Zeitschr. f. phys. Chemie, Bd. 19, 1894, S. 179. 

Biernacki : Blutkorpcrchen und Plasma in ihren gegenseitigen 
Beziehungen. Wien, med. Wochenschr., 1894, Nos. 36, 37. 

Bizzozero, G. : 1. Ueber die Bildung der roten Blutkorpcrchen. 
Virch. Arch., Bd. 95, 1884, S. 26. 2. Sulla funzione ematopoetica del 
midollo delleossa. Gazz. med. Ital.-Lomb., Novembre, 1868. 3. Ueber 
die Entstehung der rothen Blutkorpcrchen wahrend des Extrauterin- 
lebens. Moleschott's Untersuchungen zur Naturlehre, xiiL, 1888, S. 153. 

Bizzozero u. Salvioli: 1. Die Milz als Bildungsstatte rother Blut- 
kdrperchen. Centralbl. f. d. med. Wiss., 1879, No. 16. 3. Experiment. 



:384 



BIBLIOGRAPHY. 



Untersuchungen tiber die lineale Hamatopoesis. Moleschott's Uiiters., 
xii., 1881, S. 595. 

Dauioii : Leueocytlisemia, Boston, 1864. 

Ehrlich : Referat im 11 Congr. f. inn. Mediz., 1892. 

Eietihorst : Die pernicidse Anamie, Leipsic, 1878. 

Eisenlohr : Deutsch. Arch. f. klin. Med., Bd. 20, S. 495. 

Eliasberg- : Experiment. Unters. liber die Blutbildung in der Milz 
der Saugethiere. Diss., Dorpat, 1893. 

Friedreich : Virchow's Archiv, Bd. 12, S. 395. 

Gabritschewsky : Klin.-hamatolog. Notizen. Arch, fur exper. 
Pathol., Bd. 28, S. 83. 

Hamburger : 1. Ueber die Permeabihtat der rothen Blutk5rper- 
chen im Zusammenhange mit den isotonischen CoefBcienten. Zeitschr. 
f. Biol., Bd. 26, S. 414. 2. Ueber die Regelung der Blutbestandtheile 
bei ktinstUcher hydram. Plethora, Hydramie und Anhydramie. IMd., 
Bd. 27, 1890, S. 259. 3. Die osmotische Spannkraft in den medizin. 
Wissenschaften. Virch. Arch., Bd. 140, 1895, S. 503. 

Hay em, G. : 1. Du sang, etc., Paris, 1889. 2. Sur revolution des 
glob, rouges dans le sang des animaux superieurs. Compt. rend., t. 85, 
1877, p. 1285. 3. Recherches sur revolution des hematics dans le sang 
de I'homme et des vertebres. Arch, de Phys., 1878, p. 629. 

Howell, W. H. : 1. The Origin and Regeneration of Blood Corpus- 
cles. New York Med. Record, vol. xxxiv., 1888. 2. The Life History of 
the Formed Elements of the Blood, etc. Journ. of Morphol., vol. iv., 
1871, No. 1. 

Kollicker, A. Ueber die Blutkorperchen eines menschlichen Em- 
bryo und die Entwickelung der Blutk5rperchen bei Saugetieren. 
.Zeitschr. f. rat. Med., Bd. iv., 1846. 

Laache : Die Anamie, Christiania, 1883. 

Lackschewitz : Ueber die Wasseraufnahmefahigkeit der roten Blut- 
korperchen. Diss., Dorpat, 1892. 

V. Limbeck: Grundriss einer klin. Pathol, d. Blutes, Jena, 1892. 

Litten : Ueber einige Veranderungen der rothen Blutk5rperchen. 
Berl. klin. Wochenschr., 1877, No. 1. 

Litten u. Orth : Berl. klin. Wochenschr., 1877, No. 51. 

Lowit, A. : 1. Ueber die Bildung rother und weisser Blutkorper- 
chen. Prager med. Wiss., viii., 1883. 2. Dasselbe : Sitzungsber. d. 
Wien. Akad., Abth. iii., Bd. 88, 1883. 3. Ueber Blutzellenbildung 
unternormalen u. pathol. Yerhaltnissen. Prager med. Wochenschr., 
1887, No. 21. 

Manassein : Ueber die Dimensionen der rothen BlutkOrperchen 
unter verschiedenen Einflussen, Tiibingen, 1872. 

Maragliano u. Castellino : Ueber die langsame Nekrobiosis der 
rothen Blutkorperchen, sowohl in normal en, wie auch in pathol. Zu- 
standen, etc. Zeitschr. f. kl. Med., Bd. 21, S. 415. 

Mosler: Leukamie, Berlin, 1871. 

Mtiller, H. Fr.: Ueber die atypische Blutbildung bei der progr. 
pern. Anamie. D. Arch. f. klin. Med., 1893, Bd. 51, S. 282. 



BIBLIOGRAPHY. 



385 



Miiller, H. F. : Zur Frage der Blutbildung. Sitzungsber, d. Akad. 
d. Wiss. in Wien, Bd. 98, Abth. iii., 1889. 

Neumann, E. : 1, Ueber die Bedeutung des Knochenmarks fiir die 
Blutbilding. Med. Centralbl., October, 1868, S. 689. 2. Neue Beitrage 
zur Kenntniss der Blutbildung. Arch. f. Heilk., xv., S. 470,1874. 3. 
Knochenmark u. Blutkorperchen. E. Berichtigung. Arch. f. mikr. 
Anat., xii., 1876. •4. Ueber d. Entwickelung rother Blutkorper im 
neugebildeten Knochenmark. Virch. Arch., Bd. 119, 1890. 5. Ueber 
Blut regeneration u. Blutbildung. Zeitschr. f. khn. Med., Bd. 3, 1881, 
Heft 3. 6. Das Gesetz der Verbreitung des gelben und rothen Markes 
in den Extremitatenknochen. Centralbl. f. d. med. Wiss., Bd. 20, 
1882, S. 321. 

Obrastzow : 1. Z. Morphol. d. Blutbildg. im Knochenmark d. Sauge- 
thiere. Centralbl. f. d. med. Wiss., 1880, No. 24. 2. Dasselbe : Virch. 
Arch., Bd. 84, S. 358. 

Oppel, A. : Unsere Kenntnisse von der Entstehung der roten und 
weissen Blutkorperchen. Zusammenfassendes Referat. Centralbl. f. 
allg. Pathol, u. path. Anat., 1892, Bd. iii., No 5. (An exhaustive re- 
view of the most important articles on the subject.) 

Osier : Note on Cells Containing Red Blood Corpuscles. Lancet, 
1882, p. 181. 

Pouchet : La formation du sang. Revue scientif., 9 annee, No. 12, 
1879. 

Quincke : Deutsch. Arch. f. kl. Med., Bd. 20, S. 1, u. Bd. 25, S. 567. 

Rindfleisch : Ueber Knochenmark und Blutbildung. Arch. f. mikr. 
Anat., Bd. 17, 1879, S. 1. 

Schaumann : Zur Kenntniss der sog. Bothriocephalus-Anamie, 
Helsingfors, 1894. 

Vanlair u. Masius : De la microcythemie, Bruxelles, 1871. (Ref. in 
Virch. Hirsch, 1872, i., 199.) 

Winogradow: Centralbl. f. d. med. Wiss., 1882, No. 50. 

White Cells and Blood Plates. 

Afanassiew : Ueber den dritten Formbestandtheil des Blutes, etc. 
B. Arch. f. klin. Med., Bd. 35, 1884, S. 217. 

Arnold : Zur Morphologie und Biologie der Zellen des Knochen- 
marks. Virch. Arch., Bd. 140, 1895, S. 411. 

Barker, L. J. : On the Presence of Iron in the Granules of the Eo- 
sinophile Leucocytes. Bull, of the Johns Hopkins Hosp., Baltimore, 
October, 1894. 

Bizzozero: Virch. A/ch., Bd. 90. 

Botkin, S. S.: Deutsche med. Wochensch., 1892, No. 15. 
Botkin, Eugen : Leukocytolyse. Virch. Arch., Bd. 141, 1895, S. 238. 
Buchner : Berl. klin. Wochenschr., 1890, No. 47. 
Eberth u. Schimmelbusch : Die Thrombose naeh Versuchen und 
Leichenbefunden, Stuttgart, 1888. 

Ehrlich : 1. Ueber die spezifischen Granulationen de§ Blutes. Ver- 



386 



BIBLIOGRAPHY. 



handl. d. physiol. Gesellsch. zu Berlin, 1878-1879. 2. Farbenanalytische 
Unters. zur Histolog-ie u. Klinik des Blutes, Th. i., Berlin, 1891. 

Ewing : Toxic Hypoleucocytosis. New York Med. Journ., March 
3, 1895. 

Freund: Ein Beitrag zur Kenntniss der Blutgerinnung. Mediz. 
Jahrbiicher, 1886, S. 46. 

Fusari : Ref. i. Centralbl. f. inn. Med., 1887, S. 45. 

Gabritschewski : 1. Annal. de Pinst. Pasteur, 1890. 2. Mikroskc- 
pische Unters. tiber Glykogenreaktionen im Blute. Arch, f. exper. 
Path. u. Pharm., Bd. 28, 1891, S. 272. 

Goldscheider u. Jacob: Ueber die Variationen der Leukocytoses 
Zeitschr. f. khn. Med., Bd. 25, Hft. 5, 6. 

Grawitz, Paul : Atlas der patholog. Gewebelehre, Berlin, 1893. 

Gundobin : Ueber die Morphologie und Pathologic des Blutes bei 
Kindern. Jahrb. f. Kinderheilk., Bd. 35, 1893, S. 187. 

Hay em : Du sang, etc., Paris, 1889. 

Heidenhain, M.: Neue Unters. iiber die CentralkOrper. Arch. f. 
niikr. Anatom., Bd. 43, 1894. 

Hirt : Miiller's Arch., 1856, S. 174. 

Hoff meister : Ueber Resorption und Assimilation der Nahrstotfe. 
Arch. f. exper. Path., Bd. 22, 1887. 

Horbaczewski : Beitrage zur Kenntniss der Bildung der Harnsaure 
und Xanthinbasen, sowie der Leukocytosen im Thierorganismus. 
Sitzungsber. d. Kais. Akad. d. Wiss., Wien, Bd. 100, 1890, Abth. iii. 

Klein : Die diagnost. Verwerthung der Leukocytose. Volkmann's 
Samml. klin. Vortr., No. 87, 1893. 

Kossel: Deutsch. med. Wochenschr., 1894, S. 146. 

Landois : Lehrbuch der Physiologic des Menchen, Wien, 1893. 

Leber : Fortschr. d. Medizin, 1888, S. 460. 

Lilienfeld, L. : 1. Zeitschr. f. physiolog. Chemie, Bd. 20, 1895, S. 155. 
Derselbe : 2. Verhandl. d. physiolog. Gesellsch. in Berlin, 23, 10, 
1891. 

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Lowit : Ueber Neubildung und Zerfall weisser Blutkorperchen. 
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Lowit : Studien zur Physiol, u. Pathol, d. Blutes, Jena, 1892. 

Massart u. Bordet : Extrait du journal publ., Bruxelles, February, 
1890. 

Massart : Annales de I'inst. Pasteur, 1893, S. 165. 
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Wochenschr., 1893, Nos. 3, 4. 

Nikiforoff : Ziegler's Beitrage, Bd. 8, 1890, S. 400. 



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387 



Pohl : Einfluss von Arzneistoffen auf die Zahl der kreisenden 
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Posner, C: Farbenanalytische Untersuchungen. Verhandl. d. 
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Salomon, Gr. : Unters. betreffend das Vorkommen von Glykogen im 
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Schultze, Max : Arch. f. mikr. Anatomie, Bd. i., 1865, S. 38. 

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Weintraud : Ueber die Ausscheidung von Harnsaure u. Xanthin- 
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Weiss, Julius : Die Wechselbeziehungen des Blutes zu den Organen, 
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Werigo : Les globules blancs comme protecteurs du sang. Annal. 
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Wharton Jones : The Blood Corpuscles Considered in their Differ- 
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Woolridge: Die intravaskularen Gerinnungen. Du Bois' Arch., 
1886, S. 397. 

Zappert : Ueber das Vorkommen der eosinophilen Zellen im 
menschlichen Blute. Zeitschr. f. klin. Med., Bd. 23, Hft. 3, 4. 
Zenoni : Ziegler's Beitr., Bd. 16, 1894, S. 537. 

Zuntz u. Schumburg : Wissenschaftl. Versuche tiber die zulassige 
Belastung des Soldaten auf Marschen. Deutsche militararztl. Zeitsch., 
1895. Specielles tiber die Blutbefunde hierbei s. Diss, von Fr. Tornow: 
Blutveranderungen durch Marsche, Berlin, 1895. 

Secondary Anemia. 

Becquerel u. Rodier : Unters. tiber die Zusammensetzung d. Blutes. 
Deutsch von Eisenmann, Erlangen, 1845. 
Bernard, CI. : Cit. by Schenk. 

Biernacki : Unters. tiber die chemische Blutbeschaffenheit bei 
pathol., insbes. anam. Zustanden. Zeitschr. f. klin. Med., Bd. 24. 1894. 
Briicke : Lehrb. d. Physiologic. 



388 



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Bunge : Zar quantitativen Analyse d. Blutes. Zeitschr. f, Biolog., 
Bd. 12, S. 191. 

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Diabetes. 

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v. Noorden, C. : Die Zuckerkrankheit u. ihre Behandlung, Berlin, 
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Gout. 

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Neusser : Ueber einen besonderen Blutbefund bei uratischer Dia- 
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Obesity. 

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Hemorrhagic Diseases. 

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Schmidt, Alex., see Zoege v. Manteuffel. 

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Uskow : Centralbl. f. d. med. Wiss., 1878, S. 499. 
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Wright : Ref. in therapeut. Monatsh., 1892, No. 2. 
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Addison's Disease. 

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Diseases of the Stomach. 

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Betz : Ueber Hydrothionammoniamie. Memorabilien, 1864. 

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Emminghaus : Zwei Falle von mehrfacher Perforation des Verdau- 
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t 



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mens von Harnsaure u. Xanthinbasen im Blute, Berlin, 1891. 



412 



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Laache : Die Anamie, Christiania, 1883. 
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Scherer : Virchow's Arch., Bd. x., 1848. 

Schmidt, C. A. : Zur Charakteristik der epidemischen Cholera, 
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The Blood Feter. 

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Ettlinger : Etude sur le passage des microbes pathogenes dans le 
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Gartner u. Roemer : Ueber die Einwirkung von Tuberkulin und 
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Gerhardt, D. : Ueber Hydrobilirubin. Dissert., Berlin, 1889. 

Gley u. Charrin: Mitteilg. v. XL internat. Kongr. in Rom. Cen- 
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Grawitz, E. : Klinisch-experim. Blutunters, II. Zeitschr. f. kUn. 
Med., Bd. 22, 1892, Heft 4, 5. 



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413 



Hoppe-Seyler, G. : Yirch. Arch., Bd. 124, 1891, S. 30. 
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V. Limbeck u. Steindler : TJeber d. Alkalescenz-Abnahme d. Blutes 
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Lowy : Pfliiger's Arch., Bd. 58, und Centralbl. f. d. med. Wiss., 

1894, S. 785. 

Loewy u. Richter : Ueber den Einfluss von Fieber u. Leukocytose 
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Maraghano : Zeitschr. f. klin. Med., Bd. 14 u. 17. 

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Typhoid Fever. 

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Carbone : Un caso di colo-tifo. Gaz. med. di Torino, 1891, No. 23. 
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Dunin : Ueber die Ursachen eitriger Entztindungen u. Yenen- 
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Fraenkel u. Simmonds : 1. Ueber Typh. abdom. Deutsche med. 
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Gaflky : Zur Aetiologie des Abdominaltyphus. Mitteil. aus dem 
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von der Mutter zum FOtus. Centralbl. f. GynakoL, 1890, No. 46. 

Grawitz, E. : Ueber die Bedeutung des Typhusbacillennachweises 



414 



BIBLIOGRAPHY. 



fiir die klinische Diagnose des Abdominaltyphus. Charite-Annalen, 
1892, Bd. 17, S. 228. 

Halla : Zeitschr. f. Heilk., Bd. iv., S. 198. 

V. Jaksch : Ueber Diagnose und Therapie der Erkrankungen des 
Blutes. Prag. med. Wochenschr., 1890, Nos. 31-33. 

Janowski : Zur diagnost. Verwertung der Untersuchung des Blutes 
beziiglich des Vorkommens von Typhusbacillen. Centralbl. f. Bact. 
und Paras., Bd. v., 1889, No. 20. 

Kelsch : Pleur6sie determin^e par le bacille de la fifevre typhoide. 
La Sem. m^d., 1892, No. 10. 

Laache : Die Anamie, Christiana, 1883. 

Livierato : Unters. tiber die Schwankungen des Griykogen-Gehaltes 
im Blute gesunder und kranker Individuen. Deutsches Arch. f. klin. 
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V. Limbeck : Klinisches und Experimentelles tiber die entziindl. 
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Lucatello : Sulla presenza del bacillo tifoso nel sangue splenico e 
suo possibile valore. Cit. in Baumgarten's Jahresber., 1886, S. 176. 

Meisels : Ueber das Vorkommen von Typhusbacillen im Blute und 
dessen diagnost. Bedeutung. Wien. med. Wochenschrift, 1886, Nos. 
21-23. 

Menzer : Verwertung des Typhusbacillennacliweises fiir die klin. 
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Merkelu. Goldschmidt : Centralbl. f. klin. Med., 1887, No. 22. 
Neisser: Zeitschr. f. klin. Med., Bd. 23, S. 93. 

Neuhaus : Nachweis der Typhusbacillen am Lebenden. Berliner 
klin. Wochenschr., 1886, No. 6 and No. 24. 

Redtenbacher : Ueber den diagnost. Wert der Milzpunktion bei 
Typhus abdom. Zeitschr. f. klin. Med., 1891, Bd. 19. 

Rieder : Leukocytose, 1892. 

Riitimeyer : Ueber den Befund von Typhusbacillen aus dem Blute 
bei Lebenden. Centralbl. f. klin. Med., 1887, No. 9. 

Sadler : Fortschritte der Medizin, Bd. ix., 1891. 

Seitz : Bakteriol. Studien zur Typhusatiologie, Milnchen, 1886. 

Sittmann : Deutsches Arch. f. klin. Med., Bd. 53, S. 323. 

Thayer : Bulletin of Johns Hopkins Hosp., Baltimore, vol. iv., p. 30. 

Thiemich : Bakteriol. Blutunters. b. Abdominaltyphus. Deutsche 
med. Wochenschr., 1885, No. 34. 

Tumas : Deutsches Arch. f. klin. Med., Bd. 41, 1887, S. 323. 

Wiltschour : Aetiologie und klin. Bakteriologie des Typh. abdom. 
Centralbl. f. Bakt., 1890, S. 276 (Ref.). 

Asiatic Cholera. 

Biernacki : Blutbefunde bei der asiatischen Cholera. Deutsche 
med. Wochenschrift, 1895, No. 48. 

Cantani : Centralbl. f. d. med. Wissensch., 1884, S. 785. 

Hayem : Cit. by Lukjanow, Pathologic des Gefasssystems, Leip- 
zig, 1894, S. 220. 



BIBLIOGRAPHY. 



415 



Okladnych (Russian) : Cit. by Biernacki. 

Schmidt, C. A. : Zur Charakteristic der epid. Cholera. Leipzig u. 
Mitau, 1850. 

Virchow s. Rieder : Leukocytose, S. 140. 

Wlajew : Bakteriol. Untersuch. d. Bkites Cholerakranker und die 
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Petersb. med. Wochenschr., 1895 (7). 

Winter : Cit. by Lukjanow. Allg. Pathol, d. Gefasssystems, 1894, 
S. 220. 

Measles, Scarlet Fever, and Small-Pox. 

Arnheini : Ueber den Hb-Gfehalt des Blutes in einigen, vorzugs- 
weise exanthematischen Krankheiten der Kinder. Jahresber. der 
Kinderheilk., N. F.. xiii., S. 293. 

Baxter and Wilcocks : A Contribution to Clinical Hsemometry. 
Lancet, 1880. 

Brouardel : Des variations de la quantite des globules blancs dans 
le sang des varioleux, etc. Gaz. m^d. de Paris, 1874, No. 11. 

Felsenthal : Hamatol. Mitteilungen. Arch. f. Kinderheilk., xv., 
1892, S. 78. 

Halla: Zeitschr. f. Heik., 1888, Bd. iv. 

Kotschetkof f : Morphol. Veranderung des Blutes bei Scharlach. 
Wratsch, 1891, No. 41. (Ref. in St. Petersb. med. Wochenschr., 1892, 1.) 

V. Limbeck: Zeitschr. f. Heilk., Bd. x., 1890, S. 392. 

Pick : Untersuchungen tiber das quantitative Verhalten der Blut- 
korperchen bei Variola und ihren Komplikationen. Arch. f. Dermat. 
u. Syph., 1893, Bd. 25, S. 63. 

P6e: Untersuchungen tiber Leukocytose. Dissert., Berlin, 1890. 

Reinert : Zahlung der Blutkorperchen, 1891. 

Rieder: Leukocytose, 1892. 

Diphtheria. 

Beck, A. , u. Stapa, W. : Ueber den Einfluss des Diphtheriegiftes- 
auf den Kreislauf. Wien. klin. Wochenschr., 1895, S. 323. 

Bouchut et Dubrisay : Note sur la numeration des globules du 
sang dans la diphtherite. Compt. rend., vol. 85, 1877, p. 158. 

Canon: Bakteriol. Blutunters. bei Sepsis. Deutsche med. Wochen- 
schrift, 1898, No. 48. 

Cutfer: Recherches sur les alterations du sang dans quelques. 
maladies des enfants du premier age. Rev. mens., 1878, p. 519. 

Frosch : Zeitschr. f. Hygiene, 1893, Bd. xiii., Heft 3. 

Grawitz, E. : Zeitschr. f. klin. Med.. Bd. xxii.. Heft 4, 5. 

V. Limbeck : Klin. Pathologic des Blutes, 1892. 

P6e : Dissert., Berlin, 1890. 

Reinert : Blutzahlungen, 1891. 

Rieder: Leukocytose, 1892. 



416 



BIBLIOGRAPHY. 



Erysipelas, Sepsis, Pyemia, Abscess. 

Blum: Miinch. med. Wochenschr., 1893, No. 16. 

Bommers: Staphylokokkenbefund iiii Blute eines Osteomyelitis- 
kranken. Deutsche ined. Wochenschr., 1893, No. 23. 

Bond : A Contribution to the Pathology of the Blood. Lancet, 
September, 1887. 

Braidwood : On Pyaemia or Suppurative Fever, etc., London, 1868. 

Brieger : Ueber bakteriologische Unters. bei einigen Fallen von 
Puerperalfieber. Charite-Annalen, Bd. 13, S. 198. 

Brunner : Beitrage zur Aetiologie akuter Zellgewebsentziindungen. 
Wien. klin. Wochenschr., 1891, Nos. 20, 21. 

Canon: Zur Aetiologie der Sepsis, Pyamie und Osteomyelitis. 
Deutsche Zeitschr. f. Chirurgie, 1898, Bd. 37, S. 571. 

Cantu: Setticopisemia criptogenetica. Rif. med., 1892, No. 96. 

Czerniewsky : Zur Frage von den puerperalen Erkrankungen. 
Arch. f. Gynakologie, Bd. 33, 1888. 

Dennig : Ueber septische Erkrankungen mit besonderer Beriick- 
sichtigung der kryptogenetischeii Septikopyamie, Leipzig, 1891. 

Bonders : Nederl. Lane, July, 1851. 

Doyen : Etude des suppurations, etc. Progres m6d., 1886, t. iii., 
p. 222. 

V. Eiselsberg : 1. Beitrage zur Lehre von den Mikroorganismen im 
Dlute fiebernder Kranker. Wien. med. Wochenschr., 1886, Nos. 5, 8. 
2. Nachweis von Eiterkokken im Blute als diagn. Hilfsmittel. Wien. 
klin. Wochenschrift, 1890, No. 30. 

Garre : Zur Aetiologie akut eitriger Entziindungen. Fortschr. der 
Medicin, 1885, No. 6. 

V. Goetschel : Vergleichende Analyse d. Blutes gesunder u. sep- 
tisch inficierter Schafe, etc. Dissert., Dorpat, 1883. 

Grawitz, E. : 1. Beitrage zur Bakteriologie d. Blutes, etc. Charite- 
Annalen, 1894, Bd. 19. 2. The same : Klinisch-experimentelle Blutun- 
tersuchungen. Zeitschrift ftir klin. Med., 1893, Bd. 22. 3. The same : 
Hsematological Researches on the Blood in Sepsis. Internat. Clinics, 
Philadelphia, 1894. 

Hahn, Martin : Virch. Arch., Bd. 123, 1891. 

Halla: Ueber den Hb-Gehalt des Blutes und die quantitativen 
Verhaltnisse d. roten u. weissen Blutk. bei akuten fieberhaften Krank- 
heiten. Zeitschr. f. Heilk., 1883. 

Hartmann : Arch. f. Hygiene, 1887. 

Hoff : Zur Aetiologie der septischen u. pyamischen Krankheits- 
prozesse. Dissert., Strassburg, 1890. 

Huber : Correspondenzbl. f. Schweizer Aerzte, Bd. 22, 1892. 

Jordan: Die akute Osteomyelitis. Beitr. z. klin. Chir., 1893, x., 3. 

Kanthak: Acute Leucocytosis Produced by Bacterial Products. 
Brit. Med. Journ., June, 1892. 

Krebs : Beitrag zur entziindlichen Leukocytose. Dissert., Berhn, 
1893. 



BIBLIOGRAPHY. 



417 



V. Limbeck : Klin. Pathol, des Blutes, 1892. 

Manassein : Ueber die Yeranderungen in den Dimensionen der 
roten Blutkorperchen. Tubingen, 1872. 

Maragliano : Beitrag zur Pathologie des Blutes. XI. Kongr, filr 
inn. Med., 1892. 

Mobitz: Experiment. Studien tiberd. quantitativen Veranderungen 
d. Hamoglobin im Blute bei septischem Fieber. Dissert., Dorpat, 1883. 

Patrigeon : Recherches sur le nombre des globules rouges, etc., 
Paris, 1877. 

Petruschky : Unters. tiber Infektion mit pyogenen Kokken. Zeit- 
schrift f. Hygiene, Bd. 17, S. 59, and Bd. 18, S. 413, 1894. 
Pfuhl : Zeitschr. f. Hygiene. 1892, Bd. xii. 

Quincke : Ueber den Hb-Gehalt des Blutes in Krankheiten. Arch, 
f. path. Anat. u. Physiol., Bd. 54. 
Rieder : Leukocytose, 1892. 

Roscher : Blutunters. bei septischem Fieber. Dissert., Berlin, 1894. 

Rosenbach : Mikroorganismen bei den Wundinfektionskrankheiten 
des Menschen, Wiesbaden, 1884. 

Ross : Cit. in Baumgarten's Jahresber., 1889, S. 15. 

Roux et Lannois : Sur un cas d'adenie infectieuse due au staphyl. 
pyog. aur. Revue de med., 1890, No. 12. 

Sadler : Fortschritte d. Medicin, 1892. 

Sanger : Deutsche med. Wochenschr., 1889, No. 8. 

Schulten : Ergebnisse einiger Untersuchungen in Puerperalkrank- 
heiten. Virch. Arch,, Bd. 14. 

Sittmann: Bakterioskopische Blutuntersuchungen. Deutsches 
Arch. f. klin. Med., 1894, Bd. 53, S. 523. 

This contains an especially complete collection of the literature 
regarding the finding of bacteria in the blood. As regards the findings 
in the blood of the cadaver mention is made of the papers by Kar- 
linsky, Kischensky, Babes, Bonome and Bordoni-Uffreduzzi, v. Noor- 
den, Guarnieri, Pfuhl, Lenhartz, Campbell, Fischer and Levy, Gilbert 
and Girode. 

Sittmann u. Barlow : Ueber einen Befund von Bact. coli communis 
im lebenden Blute. Deutsches Arch. f. khn. Med., Bd. 52, 1894. 

Stern u. Hirschler : Beitrag zur Lehre der Mischinfektion. Wien. 
med. Presse, 1888, No. 28. 

Tilanus : Unters. iiber Mikroorganismen in einigen chirurgischen 
Krankheiten. Centralbl. f. Chirurgie, 1886, No. 13. 

Tumas : Ueber die Schwankungen der Blutk.-Zahl und des Hb-Ge- 
haltes des Blutes im Verlaufe einiger Infektionskrankheiten. Deutsch. 
Arch. f. klin. Med., 1887. 

Weichselbaum : Zur Lehre der akuten Endokarditis. Wien. med. 
Wochenschr., 1885, No. 41. 

V. Winkel : Erysipelkokken als Erreger v. Puerperalfieber. I. Kon- 
gress f. Gynakologie, 1886. 



418 



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Tuberculosis. 

Barbazzi : Centralbl. f. d. med. Wissench., 1887, No. 35. 
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Dehio : St. Petersb. med. Wochenschr., 1891, No. 1. 
Devoto : Prager Zeitsclir., Bd. xi., S. 176. 

Fenoglio, J. : Ueber die Wirkungen einiger Arzeneien auf den Hb- 
Gehalt des Blutes. Oesterreich. med. Jahrb., Heft 4, S. 635, 1882. 

Grartner u. Roemer : Wien. klin. Wochenschr., 1892, No. 2. 

Gnezda : Ueber Hamoglobinometrie. Dissert., Berhn, 1886. 

Grawitz, E. : 1. Ueber die Anamien bei Lungentuberkulose und 
Carcinose. Deutsche med. Wochenschr., 1893, No. 51. 2. Khnisch- 
experimentelle Blutunters. Zeitschr. f. kUn. Med., Bd. 21, Heft 5, 6. 

Halla : Cit. by Rieder. 

Hammerschlag : Zeitschr. f. klin. Med., Bd. 21, 1892, Heft 5, 6, S. 

475. 

Jakowski: Beitrag zur Frage tiber die sog. Mischinfektionen der 
Phthisiker, Blutuntersuchungen, etc. Centralbl. f. Bakt. u. Parasit., 
Bd. 14, 1893, No. 23, S. 762. 

Kronig : Verhandl. d. Vereins f. inn. Med., 1894 (Deutsche med. 
Wochenschr.). 

Laache : Die Anamie, 1883, S. 63. 

Laker, O. : Bestimmungen liber d. Hb-Gehalt d. Blutes mittels des 
V. Fleischl'-schen Hamometers. Wien. med. Wochenschr., 1886, Nos. 
18, 19, 25-28. 

Liebmann : Berl. klin. Woch., 1891, S. 393. (Comp. Kossel, Ibidem, 
S. 302.) 

Lustig : Wien. med. Wochenschr., 1884. 

Malassez : Recherches sur la richesse du sang en globules rouges 
chez les tuberculeux. Progres med., 1874, p. 38. 
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Nasse : Cit. by Rieder. 

Neubert, G. : Unters. des Blutes bei der, die Phthisis pulm. und 
das Carcinom begleitenden Anamie. Dissert., Dorpat, 1889. 
V. Noorden : Lehrb. d. Pathol, d. Stoffwechsels, S. 200. 
Oppenheimer : Deutsche med. Wochenschr., 1889, Nos. 42-44. 
Pasquale: Ziegler's Beitrage, Bd. xii., 1893, Heft 3. 
Peiper : Centralbl. f. klin. Med., 1891, S. 217. 

Petruschky : 1. Tuberkulose und Septikamie. Deutsche med. 
Wochenschr., 1893, No. 14. 2. Unters. tiber Infektion mit pyogenen 
Kokken. Zeitschr. f. Hygiene, Bd. xvii., 1894, S. 59. 

Reinert : Zahlung der BlutkOrperchen, 1891. 

Rieder : Leukocytose, S. 153. 

Riltimeyer: Centralbl. f. klin. Med., Bd. vi., 1885. 
Samuel : Cit. by Rieder. 

Schmaltz : Deutsches Arch. f. klin. Med.. Bd. 47, S. 145. 
ScholkofI, S. : Zur Kenntnis des spez. Gew. des Blutes unter physiol. 
u. pathol. Verhaltnissen. Dissert., Bern, 1892. 



BIBLIOGRAPHY. 



419 



Sticker : Centralbl. f. klin. Med., Bd. vi., 1885. 

Stintzing : Verhandl. des Kongr. f. inner. Med., 1893. 

Strauer : Systeiuatische Blutuntersuchungen bei Schwindstichtigen 
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1893. 

Striimpell : Mtinch. med. Wochenschr. , 1892, S. 50. 
Weichselbaum : Wien. med. Wochenschr., 1884. 

Syphilis. 

Anz : Ueber die morphol. Veranderungen des Blutes bei Syphilis. 
(Russian.) Ref. in Virch.-Hirsch's Arch., 1892, ii., S. 537. 

Bieganski : Ueber die Veranderungen des Blutes unter dem Ein- 
fluss von Syphilis u. pharmakol. Gaben von Quecksilber-Praparaten. 
Arch. f. Dermatol, u. Syphilis, 1892, S. 43. 

Gaillard : De Taction du mercure sur le sang chez les syphilitiques 
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Grassi : L'Union medic, 1857. 

Justus : Ueber durch Syphilis verursachte Blutveranderungen. 
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Laache : Die Anamie, 1883. 

Leichtenstern : Ueber den Hb-Gehalt, etc., 1878. 
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Dissert., Dorpat, 1889. 

Li^geois : Gaz. des hopitaux, 1869. 

Loos : Die Anamie bei hereditarer Syphilis. Wien. klin. Wochen- 
schrift, 1892, No. 291. 

Malassez : Arch, de phys. norm, et pathol., 1886. 

Neumann u. Konried : Eine Studie tiber die Veranderungen des 
Blutes infolge des syphil. Prozesses. Wien. klin. Wochenschr., 1893, 
No. 19. 

Rille : Ueber morphol. Veranderungen des Blutes bei Syphilis und 
einigen Dermatosen. Wien. klin. Wochenschr., 1893, No. 9. 

Schiff : Ein Beitrag zur Hamatologie der an Lues hered. u. Rachitis 
leidenden Sauglinge. Pesth. med.-chir. Presse, 1892, No. 3. 

Schlesinger : 1. Experimentelle Unters. tiber die Wirkung lange 
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Arch., Bd. 130, S. 145. 

Sorensen : Cit. by Reinert. Zahlung d. Blutkorperchen, 1891. 

Stonkowenkoff : Ueber die syphilitische und merkurielle Chlor- 
anamie. Annales de dermatol., August, 1892. 

Virchow : Die krankh. Geschwtilste, Bd. ii., S. 419. 



420 



BIBLIOGRAPHY. 



Wassermaim : Lyiiiphamie und Hauterkrankungen. Dermatol. 
Zeitchr., Bd. i. 

Wilbuscewicz : De Finfluence des i3reparations mercurielles sur le 
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Relapsing Feyer. 

Birch-Hirschfeld : Mitteil. Deutsches Arch. f. klin. Med., Bd. xiii., 
Heft 3. Schmidt's Jahrb., 106, Heft 2. 

BUesener: Ueber Febris recurrens. Dissert., BerUn, 1873. 

Bockmann: Deutsches Arch. f. kUn. Med., Bd. xxix., S. 481. 

Carter : Aspect of the Blood Spirillum in Relapsing Fever. Brit. 
Med. Journ., October 1, 1881. 

Djatschenko : Das riickkehrende Fieber. Med. Westnik (Russian), 
1875. (Cit. by Heydenreich.) 

Engel: Berl. klin. Wochenschr., 1873, No. 35. 

Heydenreich : Klin. u. mikroskop. Unters. tlber den Parasiten 
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McWeeney : Lancet, January 16, 1897. 

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2. La semaine med., 1896, p. 497. 

Metchnikoff : Annales de Finstitut Pasteur, 1891, p. 473 ; 1894, pp. 
187, 433, 714. 

Mosny and Issaeff, quoted by Widal : Compt. rend, de la soc. de 
biol., December 25, 1896. 

Moynies de Villepoix : Gazz. med. de Picardie, Amiens, 1897, No. 13. 

Nicolas : La semaine med., 1897, p. 37. 

Nicolas and Charrin : La semaine med., 1896, p, 496. 

Ohlmacher : Cleveland Med, Mag., 1896, 1897, xii., p, 86. 

Park : New York Med. Record and Med. Journal, March 27, 1897. 

Pfeifler : I. Deut. med. Wochenscr., November 29, 1894. 2. Zeit. 
f. Hyg. u. Infekt., 1894, vols. 17, 18, 19, and 21. 3, Deut. med. Woch- 
enschrift, 1896, Nos. 7, 12, and 15. 4 XIV. Congr. f. inn. Med., Wies- 
baden, April, 1896. 5. Centralbl. fiir Bakteriol, ^896, vols. 19 and 20. 

Pfeiffer and Issaeff : Deut. med. Wochenschr., March 29, 1894. 

Pfeiffer and Kolle: Deut. med. Wochenschr., November 12, 1896. 

Pick: Wien. klin. Wochenschr., 1897, No, 4. 

Puglieri : La riforma medica, Naples, 1896, vol. iv,, p. 17. 

Purjesz : Pest, med. Presse, Budapest, 1897, p. 159. 

Reed : Johns Hopkins Hospital Bulletin, March, 1897. (See also 
Thayer, ibidem). 

Rendu : Bull, et mem. de la soc. med. des hop,, December 3, 1896. 

Renon : La semaine medicale, 1897, p, 38, 

Roberts : Lancet, February 13, 1897. 



BIBLIOGRAPHY. 



429 



Robertson : Lancet, February 13, 1897. 
Rochemont : Mtinch. med. Wochensclir. , 1897, No. 5. 
Rodet : Compt. rend, de la soc. de bioL, July 31, 1896. 
Roger : Compt. rend, de la soc. de biol., July 4, 1896. 
Sabrazes : La semaine med., 1897, p. 13. 

Siredey : Bull, et mem. de la soc. m^d. d. hop., July 30, 1896. 
Soberheim : Hygien. Rundschau, 1896, No. 7. 

Stern: 1. XIV. Congr. f. inn. Med., Wiesbaden, April, 1896. 2. 
Centralbl. fiir inn. Med., Decembers, 1896. 

Stokes : New York Medical Record, January 9, 1897. 

Theolen and Mills : La clinique, Brussels, August 6 and Septem- 
ber 3, 1896. 

Thiercelin : La semaine m^d., 1896, p. 496. 

Thiercelin and Lenoble : 1. Compt. rend, de la soc. de biol., De- 
cember 11 and 18, 1896. 2. La presse med., August 5, 1896. 
Thiroloix : La presse med., 1896, No. 90. 
Thoinot : La semaine med., 1896, p. 504. 
Thomas : Medical News, April 3, 1897. 

Troisier and Sicard : Bull, et mem. de la soc. med. des hop., Jan- 
uary 21, 1897. 

Ullmann and WOhnert : New York Med. Journ., February 20, 1897. 

Vanlair and Beco : La semaine med., 1897, p. 15. 

Vedel : La semaine med., 1896, p. 312. 

Villi^s and Battle : La presse med., October 10, 1896. 

Washburn : Journ. of Path, and Bacteriol., 1895, vol. iii. 

Wassermann : Zeit. ftir Hyg. u. Infekt., 1896, p. 268. 

Weinberg : La presse medicale, Paris, 1896, p. 682. 

Widal : 1. La semaine medicale, 1896, pp. 259, 269, 295, 303, 312. 2. 
Journ. de med., July 25, 1896. 3. La presse med., Paris, July 29, 1896. 
4. Lancet, November 14, 1896. 

Widal and Sicard : 1. La semaine med., 1896, pp. 393, 410, 418, 488, 
497, 504 ; 1897, pp. 14, 21, 38, and 69. 2. La presse med., October 4, 1896. 
3. Bull, de I'acad. de med., 1896, p. 347. 4. Compt. rend, de la soc. 
de biol., December 25, 1896. 

Wright : British Medical Journal, January 16, 1897. 

Wright and Smith : Lancet, 1897, No. 10. 



INDEX. 



Abscess, 195 

of liver, 171, 253 

of lung, 207 

other forms of, 206 

pericaecal, 196 

perinephritic, 206 

subphrenic, 207 
Acetic acid, solution for counting 

white corpuscles, 17 
Actinomycosis, 93, 209 
Acute delirium, 274 

yellow atrophy of the liver, 251 
Addison's disease, 109, 277 

myelocytes in, 105 
Adenitis, 151 

tubercular, 230 
" Adult" leucocytes, 52, 53 
Agello, 281 
Albrecht, 232 
Alexander, 294 
Alkalinity, 36 

in cholera, 185 

in diabetes, 274 

in fever, 159 

in gout, 275 

in osteomalacia, 279 

in rheumatism, 181 
Alt and Weiss, 342 
Altitude, effect on blood, 65 
Amyloid disease, 151 
AnasQiia, 68 

causes of, 80 

classification of, in infancy, 338 
color of skin and mucous mem- 
branes in, 68 
destruction of corpuscles in, 74 
due to intestinal parasites, 333 
in infancy, 337 

infantum pseudoleuksemica, 341 
in gastric atrophy, 242 
leucocytosis in, 338 
myelocytes in, 104 
nucleated red cells in, 75 
pernicious, 117-132 
post-febrile, 167 
primary and secondary, 69 
red corpuscles in, 71 



Anaemia, stages in secondary, 71 
splenic hyperplasia in, 337 
white cells in (see Leucocytosis) 

Andeoud, 242 

Ankylostoma duodenale, 333 
Antipyretics, effect on leucocytes, 
160 

effect on red cells, 158, 284 
Antipj'rin, eosinophilia from, 102 

leucocytosis from, 96 
Aoyoma, 209 
Appendicitis, 195-201 
Arnold, 104 

Arthritis, gonorrhoeal, 184 

septic, 184 
Asiatic cholera, 184 
Askanazy, 79, 333 
Asthma, bronchial, 268 

cardio-renal, 269 

Bacteria in blood, 333 

in blood of sepsis, 189 
Bacteriological examination of the 

blood, 35, 36 
Badt, 251 
Baginsky, 342 
Barlow's disease, 281 
Basedow 's disease, 277. (See Graves' 
Disease. ) 

eosinophilia in, 101 

lymphocytosis in, 101 

myelocytes in, 104 
Basophilic cells, 52 

granules, Neusser's perinuclear, 
348 
Behier, 110 
Belfanti, 159 
Below, 45 , 
Beri-beri, 93 
Bieganski, 163 
Bierfreund, 290, 311 
Bignami and Dionisi, 325 
Bilharz, 333 

Billings, 161, 163, 165, 173, 326 
Binz, 95 

Blood, bacteriological examination 
of, 35, 333 



INDEX. 



431 



Blood, counting, 10 
crises, 111 
destruction, 281 
examination of dried and 

stained, 47 
examination of fresh, 5 
examination, value of, 3 
in infancy, 835 

normal appearances of, 9, 38, 47 

plates, 41, 46 
Blum, 189 
Bommers, 189 

Bone diseases, eosinophilia in, 100 

tuberculosis, 223, 105 
Bothriocephalus latus, 333 
Bouchut, 174, 281 
Boulay, 159 
Brain diseases, 271 
Brandenburg, 283 
Bronchitis, 164, 169, 266 

acute, 266 

chronic, 268 
Brownian motion, 9, 317 
Brunner, 189 
Bubonic plague, 209 
Burns, haemoglobinsemia in, 283 

myelocytes in, 105 

Cabot, 109 

Cachexia, cancerous, red cells in, 

73, 287 
Cancer, 287 

anaemia in, 290 

effect of metastases in, 299 

lack of anaemia in, 290 

leucocytes in, 298 

effect of position of, 294 

of breast, 295 

of gullet, 800 

of intestine, 301 

of kidney, 303 

of liver, 801 

of omentum, 802 

of stomach, 296 

of uterus, 803 

percentage of haemoglobin in, 
290 

Capps, 58, 104, 271, 299 
Carbonic acid poisoning, 66,104,284 
Carcinoma (see Cancer). 
Carmichael, 258 
Castration, effects of, 100, 102 
Cell death, prevention of, 8 
Celli and Guarnieri, 74 
Cerebral disease (see Brain) . 
Cerebral hemorrhage, 111, 216 

tumors, 216, 271 
Charcot-Leyden crystals, 147 
Cheron, 63 



Childbirth, influence on red cells, 
44 

influence on white cells, 87 

Chloroform -benzol, use of, in esti- 
mating specific gravity, 30 

Chlorosis, 132-138 

haemoglobin in, 133 
infantile, 389 
myelocytes in, 104 
red cells in, 133-137 
specific gravity in, 137 
white cells in, 187, 138 

Cholsemia, 252 

Cholangitis, 247, 258 

Cholera, Asiatic, 184 

Chorea, 271 

Christol, 209 

Chrobak, 279 

Cirrhotic liver, 247 

changes in red cells in, 64, 74 
hypertrophic forms of, 249 

Coagulation, 87, 287 

Cold, effects of, 44, 87 

Colic, hepatic and renal, 201, 252, 
265 

intestinal, 201 
Colitis, 244 

Color of blood in chlorosis, 133 
of blood in leukaemia, 140 
of blood in pernicious anaemia, 
117 

of skin in anaemia, 68 
Color index, 106, 122, 134, 239, 292 
Coma, blood in, 216 
Concentration of blood, 44, 62, 256 
Convulsions, leucocytes in, 272 
Cornil's "Markcells," 57 
Counting, difficulties of, 15 

of red cells, 10-17 

of white cells, 17-20 
Cover-glasses, cleaning of, 7, 32 

method of holding, 7 

necessity of cleanliness, 7 

preparations, 32 
Crenation, 39, 72 
Crocq, 342 
Curtis, 201 

Cyanosis, general, effect on blood, 
60, 256 

local. 60 
Cysticercosis, 271 
Cystitis, leucocytes in, 98, 169 

myelocytes in, 105 
Czerniewsky, 189 

Da Costa, 285 
Daland, 21 
Dane, 228 

Debility, effect on red cells, 278 



432 



INDEX. 



Debility, effect on white cells, 53, 
54, 98 

Degenerative changes in red cells, 

40, 50 
Dermatitis, 94 
Diabetes, 2?4 

myelocytes in, 104 
Diabetic coma, 216 
Diarrhoea, concentration of the 
blood in, 62 

chronic, 244 
Dieulafoy, 166 

Differential counting, method of, 34 
Digestion leucocytosis, 83 

leucocytosis in gastric cancer, 
298 

leucocytosis in gastric catarrh, 
241 

leucocytosis in gastric ulcer, 238 
Dilatation of the stomach, 243 
Dilution of the blood, 11, 44, 64 
Diphtheria, 172 

effects of antitoxin, 173 

leucocytosis in, 174 

lymphocytosis in, 176 

myelocytes in, 175 

red corpuscles in, 172 
Distomum haematobium, 333 
Dried preparations of blood, 32 

preparations of blood, red cells 
in, 47 

preparations of blood, white celJs 

in, 48 

residue of blood, estimation of, 
• 237 

Duodenal ulcer, 240, 283 
Dysentery, 244 
Dyspepsia, 240 

Ear, puncturing the, 6 
Eaton, 285 
Ebstein, 344 
Eczema, 94 

Effusions, serous, 62, 210 
Ehrlich, 146 
Eiselberg, 189 
Emphysema, 268 
Empyema, 213 
Endocarditis, 254 

ulcerative, 188, 254 
Endoglobular changes in red cells, 72 
Engel, 104, 176, 346 
Enteritis, acute, 241, 244 

chronic, 244 
Eosinophilia 100-102, 138, 178, 208, 

268, 305, 311 
Eosinophiles, appearance in fresh 
blood, 40 

appearance in stained blood, 51 



Eosinophiles, in malignant disease, 
305, 311 

in normal blood, 53 

life history of, 54 
Eosinophilic myelocytes, 57, 146 
Epilepsy, coma after, 216 

red cells in, 74 

white cells in, 102, 272 
Epstein, 342, 343 
Erysipelas, 74, 185 
Escherich, 300 
Etat cribriforme, 248 
Everard, 209 
Ewing, 174, 209 
Exercise, effect on blood, 44 

Fjecal impaction, 202 
Fatigue, effects on blood, 45 
Fede, 342 
Felon, 93, 206 

Felsenthal, 174, 178, 179, 342, 344 
Fever, influence on the blood, 158 
Fibrin network, 41, 42 

network, general pathology of, 
107, 108 

network, in cancer, 287 
Fick, 66 

Filaria sanguinis hominis, 326 

sanguinis hominis, examina- 
tion for, 327 
Fink, 268 
Finlay, 208 

Fischel, 337, 342, 344, 347 
Fixation of blood films by alcohol 
and ether, 32 
of blood films by heat, 32, 33 
Fleischer and Penzoldt, 154 
Fleischl's hsemometer, 25-29 
Floating kidnev, 202 
Frankel, 147, 152 
Furunculosis, 93 

Gabritschewsky, 174, 268 
Gaillard, 232 
Gall-stones, 252 
Garrod, 180 

Gas, illuminating, poisoning by, 66, 

94, 104, 284 
Gastric cancer, 296 

dilatation, 243 

ulcer, 237 
Gastritis, 240 

chronic, 241 

corrosive, 243 
Gastro-enteritis, 239, 241 
General paralysis of the insane, 104, 
271 

Genitals, influence on blood, 100, 
101 



INDEX. 



Gibson, 258 
Gilbert, 146, 252 
Glanders, 209 
Glands (see Adenitis) 
Goldschneider and Jacob, 95, 153, 
159 

Gollasch, 268 
Gonorrhoea, 101, 207 
Gout, 275 

Gowers' solution, 11 

Graves' disease, 277 

Gravity, specific, method of esti- 
mating, 30. 31, 108 

Grawitz, 130, 159, 172, 189, 237, 245, 
246, 247, 248, 251, 254, 256, 260, 

262, 264, 265, 268, 274, 275, 290, 
295, 325, 326 

Grippe, 96, 187, 243 
Guniprecht, 108 

Habershon, 275 
Haematocrit, accuracy of, 21 

advantages of, 21 

method of using, 22-25 
Haematology, 3 
Hsemocytolysis, 282 
Haemoglobin, estimation of, 25-29 

general pathology of, 106 

in chlorosis, 133 

indirect estimation of, by spe- 
cific gravity, 31 

in malignant disease, 290, 309 

in pernicious anaemia, 118 
Haemoglobinaemia, 74, 191, 282 

paroxysmal, 283 
Haemophilia, 6, 282 
Hemorrhage, 91, 109 
Hemorrhagic diseases, 281 
Halla, 165, 186, 210 
Hammerschlag, 29, 104, 129, 247 
Hanot and Menier, 250 
Hare, 161 
Hartuug, 299 
Hay, 243 

Hayem, 25, 107, 133, 136, 166, 177, 
180, 181, 210, 215, 246, 247, 248, 
249, 250, 251, 257, 260, 261, 262, 

263, 264, 281, 295, 301, 303, 304, 
307, 339, 341, 345 

Heart, diseases of, 254 
diseases of, aortic, 258 
diseases of, concentration of 

blood in, 256 
diseases of, congenital, 258 
diseases of, dilution of blood in, 

257 

diseases of, leucocytes in, 257 
diseases of, mitral, 258 
Hedin, 21 



Henck, 153 
Henry, 230 
Herpes zoster, 94 

Hock and Schlesinger, 279, 336, 339, 
342 

Hodgkin's disease, 154 
disease in infancy, 343 
disease, myelocytes in, 157 
disease, transition to leukaemia, 
154 

disease, white cells in, 157 
Hoff, 189 
Hofmeier, 247 
Holmes, 104, 223 
Houston, 273 
Hydatid, 207, 251 
Hydraemia, 68, 80 
Hydronephrosis, 151 
Hyperacidity and hypersecretion, 
242 

Hypochondriasis, 272 
Hysteria, 101, 216, 272 

Icterus of the new-born, 247 
Illuminating gas, poisoning by, 284 
Infancy, anaemias of, 337 

blood in, 335 

eosinophilia in, 100, 101 

haemoglobin in, 336 

leukaemia in, 346 

lymphocytosis in, 98 
Influenza, 187 
Insanity, anaemia in, 273 

eosinophilia in acute, 102, 273 
Intestine, cancer of, 302 

diseases of, 243 

obstruction of, 245 
Isotonia, isotonic coefficient, 37 

V. Jaksch, 108, 161, 165, 216,251,271, 
277, 278, 279, 332, 338, 339, 341, 
342, 343, 344, 345, 346 
Jaundice, catarrhal, changes of red 
cells in, 74 
catarrhal, increased resistance 

of red cells in, 246 
catarrhal, volume of red cells in, 
246 

in pneumonia, 160 
Jones, 208 
Justus, 233 

Kanthak, 192 

Kelsch, 325 

Khetagurow, 167 

Kidney, cancer of, 303 
diseases of, 259 
diseases of, acute, 260 
diseases of, chronic, 261 



434 



INDEX. 



Kidney, floating, 202, 266 
floating, cyst of, 151, 207 
stone in the, 265 

Kiener, 209 

Kilodse, 165 

Kisch, 274 

Klein, 100, 104. 342 

Koblank, 258, 260, 261, 2«2, 263 

Konried, 231 

Koppe, 65 ' 

Kotschetkoff, 178 

Kovak, 153 

Kraepelon, 276 

Krebs, 104, 192, 255 

Kronig, 284 

Krypiakiewicz, 273 

Kussmaul, 243 

Laache, 234, 297 

Lactation, influence on red cells, 44 
Lactic acid, in blood of rheumatism, 

18.1 
Laehr, 165 
Laker, 112, 291, 307 
Lannois, 189 

Lead encephalopathy, 216 

poisoning, changes of red cells 
in, 74 
Le Breton, 276, 277 
Leichtenstern, 268 

and Wick, 62 
Leprosy, 234 
Letzius, 232 
Leucocytosis, 81 

absenceof, 96 

after cold baths, exercise, 

massage, 87 
after parturition, 87 
definition of, 81 
diagnostic value of, 85 
from therapeutic influences, 

95 

in infancy, 84, 338 

inflammatory, 91-94 

of digestion, 83, 238, 241, 298 

of malignant disease, 293, 309 

of pregnancy, 86 

of the moribund, 90 

of the new-born, 86, 335 

pathological, 90-98 

physiological, 83-90 

post-hemorrhagic, 91 

toxic, 94 
Leucopenia, 97 

in anaemia, 97 

in infectious diseases, 97 

in starvation, 97 
Leukaemia, 140-154, 344-346 

adult leucocytes in, 145 



Leukaemia, anaemia in, 142 

Charcot-Leyden crystals in, 147 
effects of intercurrent infec- 
tions in, 152 
eosinophiles in, 100, 146 
haemoglobin in, 141 
in infancy, 344 
lymphatic, 147 
lymphocytes in, 146, 148 
megaloblasts in, 142, 148 
myelocytes in, 143, 146 
Neusser's granules in, 147 
normoblasts in, 142, 148 
red corpuscles in, 74, 141, 148 
septicaemia in, 149 
splenic -myelogenous, 140-147 
white cells in, 142, 148 

V. Limbeck, 64, 66, 74, 210, 215, 227, 
228, 246, 248, 250, 251, 257, 266, 
279, 285, 287, 295, 307, 336, 343, 344 

Lindstrom, 122 

Lipaemia, 108, 274 

Litten, 123, 149 

Liver, abscess of, 253 

acute yellow atrophy of, 94, 251 
cancer, 301 
cirrhosis, 247-249 
cholangitis, 247; 253 
diseases of the, 246 
gumma, 254 
hydatid of, 251 

Loos, 104, 339 

Lowitt, 95 

Lungs, diseases of, 266 

Luzet, 279, 337, 339, 341, 342, 343, 345 

Lymphocytes, appearances of, 48 

percentage among white cells, 53 
Lymphocytosis, 98 

in chlorosis, 98, 138 

in Graves' disease, 98, 101, 277 

in infancy, 98, 335 

in leukaemia, 146-148 

in malignant disease, 304, 310 

in pernicious anaemia, 98, 127 

in pneumonia, 99, 163 

in rickets, 279 

in syphilis, 98, 233, 335 

in thyroid feeding, 99 

in typhoid fever, 170 

Malaria, 181 

absence of leucocytosis in, 96 
blood destruction in, 74 
haemoglobinaemia in, 283 
haemoglobin in, 325 
myelocytes in, 105 
parasite of, 315 

parasite of, crescentic forms, 321 
parasite of, flagellate forms, 321 



INDEX. 



435 



Malaria, parasite of, hyaline forms, 
316 

parasite of, pigmented forms, 
317 

parasite of, segmenting forms, 
319 

preparation of stained speci- 
mens, 323 

red cells in, 74, 324 

white cells in, 326 
Malignant disease, 287. See Cancer 
and Sarcoma. 

disease, differential diagnosis 
of, 313 

disease, summary of blood - 
changes in, 312 
Manson, 329, 330 

Maragliano, 71, 73, 74, 124, 136, 158, 

181, 247, 248 
Marrow, eosinophiles in, 54 

myelocytes in, 55 
May, 222, 223 
Measles, 179 

leucocytes in, 96, 179 

red cells in, 74, 179 
Measuring corpuscles, 42 
Megaloblasts, 76 

in chlorosis, 136 

in malignant disease, 298 

in parasitic anaemia, 334 

in pernicious anaemia, 124 

in secondary anaemia, 79 
Melan^mia, 109, 278 
Meningitis, 215 

cerebro-spinal, 216 

tubercular, 228 
Menstruation, effect on red cells, 44 

eosinophiles in, 101 
Microblasts, 79 
Mikulicz, 112, 291 
Mitchell, 63, 89, 122 
Mitosis, 54 
Mocyntkowsky, 332 
Molecular motion in corpuscles, 9, 
39, 317 

Mononuclear neutrophiles, 50, 51, 58 
Monti and Berggriin^ 160, 279, 337, 

338, 339, 340, 342, 343 
Morse, 174, 345, 346, 347 
Movable stage, use of, in differential 

counting, 34 
Mozler, 154 

Miiller, 152, 153, 234, 268, 298 
Mumps, 179 
Miinzer and Palmer, 66 
Murray, 276 
Mya and Sanarelli, 74 
Myelocytes, 55-58, 103-106 
in cancer, 305 



Myelocytes, in leukaemia, 144 
in other conditions, 104, 105 
in pernicious anaemia, 128 
in sarcoma, 311 

Myocarditis, 256 

Necrobiosis of red cells, 71 
Nephritis, 260 

acute, 260 

chronic, 262 

chronic chronic diffuse, 261 
chronic interstitial, 264 
parenchymatous, 261 
necrobiotic changes in, 73 
red cells in, 74, 260 

Nervous system, diseases of, 270 

Netter, 252 

Neubert, 289 

Neumann, 277 

Neuralgia, 271 

Neuritis, alcoholic, 270 
acute multiple, 270 

Neusser, 100, 104, 222, 275, 277, 279 

Neusser's granules, 222, 348 

Neutrophilic granules, 50, 55 

Newton's rings, 13 

V. Noorden, 111, 247, 268. 274 

Normoblasts, 75, 79 
in chlorosis, 136 
in infantile blood, 336 
in pernicious anaemia, 124 
in secondary anaemia, 79 

Nuclein, eosinophilia from, 102 
leucocytosis from, 95 

Nucleated red corpuscles, 75 

red corpuscles, atypical forms 
of, 77 

red corpuscles in anaemia of in- 
fants, 340 

red corpuscles in chlorosis, 136 

red corpuscles in malignant dis- 
ease, 293 

red corpuscles in pernicious an- 
aemia, 126 

red corpuscles in tuberculosis, 
218 

Nutrition, effects on blood, 44, 45 

Obermeyer, 331 
Obesity, 274 

Obstruction, intestinal, 245 
Oertel, 27 
Oliver, 63 

Omentum, cancer of, 302 
Operations, 

surgical, contraindications in 

the blood, 112 
surgical, effect on leucocytes in 
cancer, 296 



436 



INDEX. 



Operations, surgical, loss of blood 

in, 110 
Oppenheimer, 237, 277 
Orion, 187 

Osier, 181, 215, 281, 345, 346 
Osteomalacia, 278 

eosinophiles in, 100 

mvelocvtes, in, 104 
Osteomyelitis, 101, 105, 205 

tubercular, 225 
Osteosarcoma, 309 
Osterspey, 135, 239, 289, 297, 301 
Otitis media, 169, 205 
Ouskow, 170, 281 

Pachymeningitis hemorrhagica, 
271 

Parasites of the blood, 315 

intestinal, influence on the 

blood. 333 
malarial (see Malaria) 

Paresis, 271 

Pee, 180, 186, 255, 300 

Pellagra, eosinophilia in, 100 

Pelvic abscess, 203 
neuralgia, 201 

Pemphigus, eosinophilia in, 100 

Penzoldt, 259 

Pericarditis, serous, 214 
tubercular, 230 

Perinuclear basophilia, 222, 348 

Peritonitis, 200, 213 
general septic, 214 
granular, 214 
pelvic, 203 
tubercular, 227 

Pernicious anaemia, 117 

anaemia, changes of red cells in, 

74, 118,123, 124 
anaemia, diagnosis of, 129 
anaemia, eosinophiles in, 128 
anaemia, haemoglobin in, 122 
anaemia in infancy 343, 344 
anaemia, lymphocytes in, 127 
anaemia, megaloblasts in, 126 
anaemia, myelocytes in, 128 
anaemia, necrobiotic changes in, 
73 

anaemia, relapse in, 118, 120 
anaemia, white cells in, 120 

Perspiration, effect on blood, 44 

Petrowsky, 258 

Petruschky, 189 

Phenacetin poisoning, 284 

Phlebitis, 169 

Phosphorous poisoning, 65, 66, 102, 
251 

Phthisis, 217 

anaemia of, 217 



Phthisis, eosinophiles in, 102, 222 
fibroid, 220 

myelocytes in, 104, 222 

white corpuscles in, 219 
Physiology of blood, 38-58 
Pick, 161, 180, 186, 229 
Pipette (see Thoma-Zeiss) 

cleaning of, 16 
Pilocarpine, leucocytosis after, 96 
Plague, bubonic, 209 
Plethora, 59-62 

possibility of a true, 66 
Pleurisy, 210 

purulent, 213 

serous, 210 

tubercular, 211, 230 
Pneumonia, 159 

artificial production of leuco 
cytosis in, 161 

bacteriology of blood in, 159 

coagulation in, 159 

leucocytes in, 160 

prognosis in, 160 

red cells in, 160 
Pohl, 95 

Poikilocytosis, 72 

Polychromatophilic changes in 

pernicious anaemia, 124 
Polycythaemia 59-61, 65 
Polymorphonuclear cells, 49, 50, 53, 

145 

Porter, C. B. , 194 • 
Potain, 297 

Potassium, chlorate of, poisoning 

by, 283 
Pregnancy, 44 

extra-uterine, 202 
Puerperal mania, 274 

mania, myelocytes in, 104 
Puncture of the ear in blood exam- 
ination, 5 
Purgation, concentration of the 

blood in, 62, 243 
Purpura, 281 

changes of red cells in, 74 

necrobiotic changes in, 73 
Pus tube, 203 « 
Putnam, 276 
Pyaemia, 188 

changes of red cells in, 74 
Pyelo-nephritis, 265 

Quincke, 118 

Quinine, effect on blood in fever, 158 
poisoning, leucocytes of, 94 

Ratio of red to white cells, estima- 
tion in fresh blood, 9 
of red to white cells, estimation 
in stained specimens, 47 



INDEX. 



437 



Raudnitz, 342, 344 

Regeneration of blood after hemor- 
rhage, 110 
of blood after operation for can- 
cer, 291 

Reinbach, 291, 301, 304, 308, 311 
Reinert, 4, 15, 22, 157, 262, 273, 282, 

289, 297 
Reiss, 231 
Rendu, 166 

Resistance of blood to water, elec- 
tricity, etc., 37 
Rheumatism, acute articular, 180 

chronic articular, 183 

muscular, 183 

red cells in, 181 

subacute, 183 

white cells in, 182 
Rickets, 279 

anaemia in, 279, 339 

leucocytosis in, 280 

lymphocytosis in, 98, 280 

myelocytes in, 105, 280 
Rieder, 20, 138, 163, 165, 175, 178, 
179, 187, 210, 215, 227, 255, 291, 
295, 297, 309 
Ritchie, 279 
Roscher, 190, 255 
Rosenstein, 248 
Rotch, 229, 342, 344, 346 
Rotheln, 96, 180 
Rouleaux formation, 38 
Roux, 189 
Rovighi, 89 
Roy, 29 

Sadler, 192, 257, 260, 261, 262, 263, 
295, 297, 309 

Saline cathartics, influence of, on 
the blood 243 
solution, normal, 111 

Sanger, 189 

Sarcoma, 307 

anaemia in, 307 
eosinophilia in, 100, 811 
leucocytes in, 309 
myelocytes in, 104, 311 

Saussure, 329 

Scarlet fever, 177 

changes of red cells in, 74 
eosinophilia in, 178 
leucocytosis in, 177 
necrobiotic changes in, 73 

Schaumann, 333 

Schiff, 84, 336 

Schneyer, 292, 295, 298 

Schneider, 257, 294, 297 

Screiber, 57, 268, 293 

Schultz, 87 



Schwerskewski, 268 
Scurvy, 281 

lymphocytosis in, 98 
Secondary anaemia, 68-80 

causes of, 80 

grades of, 79 

Maragliano's degenerative 
changes in, 71 

nucleated red corpuscles in, 75 
Senator, 154, 342 
Sepsis, 192 

bacteria in blood of, 189 

in leukaemia, 149 

in wounds, 192 

leucocytes in, 190 

myelocytes in, 105 

puerperal, 191 

red cells in, 190 

streptococcus, 193 
Sero-diagnosis, 663 

in cholera, 373 

in colon-bacillus infections, 374 

in diphtheria, 373 

in hog cholera, 375 

in Malta fever, 375 

in peripneumonia of cattle, 375 

in pneumococcus infections, 373 

in proteus infections, 375 

in psittacosis, 376 

in pyocyaneus infections, 373 

in scarlet fever, 376 

in septicaemia, 373 

in tetanus, 376 

in thrush, 375 

in typhoid, 363 
Sero-prognosis, 378 
Serum, examination of, 356 

clump reaction, general descrip- 
tion, 349 

clump-reaction technique, 351 

clump reaction, theory of, 376 

dried blood, use of, 353 

cultures, how prepared, 358 

dilution and the time limit, 
361 

fluid blood, use of, 352 
fluid serum, use of, 355 

Shattuck, 118, 164, 184, 347 

Silberman, 247 

Sittmann, 159, 189, 252, 254 

Skin diseases, eosinophilia in, 100, 
101 

Small-pox, 180 

leucocytes in, 180 

pneumonia in, 161 

red cells in, 73, 180 
Smith, 273 

Solids, estimation of, in blood, 37 

Sorensen, 229 



9 



438 INDEX. 



Spinal cord, chronic diseases of, 271 
Spirocheete of relapsing fever, 331 
Spleen, hypertrophy of, in rickets 

and all anaemias of infancy, 

385 

tumors of. 102 
Staining, Biondi-Heidenhain form- 
ula, 33 

Ehrlich-Biondi formula, 33 
fluid, Ehrlich's latest, 33 
mast-cells, 52 

Neusser's perinuclear basophilic 
granules, Appendix. 

of red cells when degenerated, 73 

the malarial parasite, 322 
Starvation, effects of, on blood, 45, 62 
Sternberg, 279 
Stomach, 238 

cancer of, 296 

channels of. influence on blood, 

238 

dilatation of. 243 

inflammation of, 240 

ulcer of, 237 
Stone, 68. 146 
Strauer, 292. 295 
Striimpell, 146 

Suprarenal extract, concentration 

of blood by, 63 
Surgerv, value of blood examina- 

tionsin, 112, 194, 198, 200, 291 
Sweating, concentration of blood 

in, 62 

Svm pathetic nervous system, in- 

'fluence on blood of, 100. 102 
Syphilis, 231 

anasmia in. 231, and 339 seg. 

cerebral, 271 

changes of red cells in. 74 
effects of mercury on tlie blood 

in, 232 
eosinophilia in, 102. 234 
hasmoglobin in, 233 
leucocytosis in, 233 
lymphocytosis in, 98 
myelocytes in, 104, 234 

Taussig. 251 

Thaver, 87, 133. 138, 167, 319, 324, 
347 

Tlioma-Zeiss blood counter, ac- 
curacy of, 15, 21 
blood counter, cleaning of, 16 
blood counter, disadvantages, 21 
blood counter, use of. 10-20 
counting slide, 14 

Thomas. 277 

Toeniessen. 258 



Toisson's solution, 11 

Tonsillitis, 186 

Townsend, 68 

Toxic leucocytosis, 94 

Transitional ieucocvtes, 49 

Treves, 201 

Trichinosis, 209 

eosinophilia in. 102 
Tropical anaemia, 69 
Tschirkoff, 109, 278 
Tubercular pneumonia, 220 
Tuberculin. 102, 220 
Tuberculosis, 217 

acute miliary, 225 

changes in red cells in, 74, 217, 
340 

genito urinary, 231 

leucopenia in. 226 

Ieucocvtes in. 97, 219. 221, 223, 

226, 228 
of bones, 223-225 
of serous membranes, 227 
pulmonary, 219 
Tumas, 208 

Tumors (see Cancer and Sarcoma) 
Typhoid, 165 

anaemia in, 166 

bacteriology, 165 

changes of red cells in, 74 

diagnosis of, 171 

effects of complications, 169 

effects of intestinal perforation 
in, 169 

leucocytosis in, 168 

leucopenia in, 97, 168 

serum-diagnosis in, 166 
Typhus, 208 

necrobiotic changes in, 73 

Ur.^:mia, 216 

Uric-acid diathesis, 223, 275 
Urine, examination of, compared 

with blood examination, 3 
Uterus, cancer of, 303 

Vasomotor influences, effect on 

blood, 44, 60 
Volume of red cells estimated by 

haematocrit, 21 
Vomiting, concentration of blood 

in, 62 

Warm-stage, use of, 8 

Warren, J. C, 194 

Warthin, 226. 285 

Weintraub. 74, 247 

Weiss. 100 

Welch, 297 

White, Franklin. 19 



INDEX. 



439 



White corpuscles, amoeboid and 
non -amoeboid forms, 40 
corpuscles, description of, in 

fresh blood, 40 
corpuscles, distinguishing them 

from red, 16 
corpuscles, normal number of, 46 
Widal, 166 
Wilks, 209 
Winiarski, 234 



Wlajew, 248 
Wounds, septic, 192 

Xanthin bases, effect of, in blood, 
101, 102, 223 

Yellow fever, 208 

Zappert. 100, 178, 215, 271, 277 
Zeissl, 150, 153 



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